Mesothelial cells can detach from the mesentery and differentiate into macrophage-like cells

Peritoneal cell suspension is composed of heterogeneous cell population. Macrophages are the most numerous cells among them. They can originate from different sources and can be resident, exudate and elicited. When we used Freund's adjuvant to elicit peritoneal macrophages, cells having large amount of caveolae on their plasma membrane appeared in the peritoneal wash. The number of these caveolae-rich cells increased by the time of the Freund's adjuvant treatment. Although their morphology was different form from the common macrophages, they were labelled with pan-macrophage antibodies. As the origin of these cells is unknown in this work, we tried to find out where they can originate from. Our interest turned towards the mesothelial cells. We found that the adjuvant treatment resulted in significant morphological changes in these cells and stimulate them to leave the surface of the mesentery. By the time of the adjuvant treatment, the macrophage markers expression increased in the mesothelial cells and more cells were found to detach from the mesentery. These results strongly suggest that under special stimuli mesothelial cells can leave the mesentery and differentiate into phagocytotic (macrophage-like) cells. These data raises the idea that mesothelial cells might not entirely differentiated and represent a multipotential cell lineage. To study whether this is the case we used anti-nestin antibody, which is a specific marker for multifunctional, multi-lineage progenitor cells. Mesothelial cells showed strong labelling with this antibody indicating that these cells really represent a 'young', not entirely differentiated cell population.     

Characterization of peritoneal leukemia-associated macrophages in Notch1-induced mouse T cell acute lymphoblastic leukemia

Macrophages, which have remarkable plasticity, are indispensable cellular components and play essential roles in both innate and adaptive immune responses. Peritoneal macrophages show unique gene expression profile and peritoneal cavity is also involved in leukemia. However, the characteristics of peritoneal leukemia-associated macrophages (Per LAMs) have not been established. Here we studied the phenotype of Per LAMs, their subpopulations in Notch1-induced acute lymphoblastic leukemia mice and compared with LAMs from BM or spleen in the same model. Peritoneal macrophages and Per LAMs simultaneously expressed high level iNOS and Arg1, which was not commonly observed in macrophages from different origins. Furthermore, LAMs from peritoneal, BM and spleen expressed lower level CSF-1, TGF-β1 and VEGF-A than tumor-associated macrophages (TAMs). Moreover, diverse responses in the expression of some phenotype-associated genes to leukemia microenvironments were detected among those LAMs. In addition, Per LAMs can be sub-divided into CD206⁺ and CD206⁻ sub-populations, which expressed both M1- and M2-associated genes. These results revealed the unique phenotype of Per macrophages and Per LAMs and contributed to better understanding of macrophage plasticity and their pathological roles in leukemia.     

The peritoneal environment in endometriosis

The local environment of peritoneal fluid (PF) surrounding the endometriotic implant is immunologically dynamic and links the reproductive and immune systems. Peritoneal fluid contains a variety of free floating cells, including macrophages, mesothelial cells, lymphocytes, eosinophils and mast cells. Macrophages are attracted to the peritoneal environment more abundantly than any other cell type. These scavengers promote cellular growth and viability through secretion of growth factors and cytokines. It is now becoming evident that cytokines play an important role in reproduction at various levels, including gamete function, fertilization and embryo development, implantation and postimplantation survival of the conceptus. Peritoneal fluid has been shown to affect negatively ovum capture by the fimbria, sperm survival, spermatozoon-oocyte interaction and embryonic development. We have recently identified the presence of two pro-inflammatory chemoattractant cytokines for monocyte/macrophages (MCP-1) and for granulocytes (interleukin-8, IL-8) in the PF. Concentrations of both IL-8 and MCP-1 are not only elevated in PF of women with endometriosis compared to those without endometriosis, but they are related to the severity of the disease. Over the past 70 years, at least a dozen theories have been proposed to explain the histogenesis and aetiology of endometriosis. It appears that the aetiology is multifactorial, and today a composite theory of retrograde menstruation with implantation of endometrial fragments in conjunction with peritoneal factors to stimulate cell growth is the most widely accepted explanation for peritoneal endometriosis.     

Liposomes of phosphatidylcholine and cholesterol induce an M2-like macrophage phenotype reprogrammable to M1 pattern with the involvement of B-1 cells

Macrophages respond to endogenous and non-self stimuli acquiring the M1 or M2 phenotypes, corresponding to classical or alternative activation, respectively. The role of B-1 cells in the regulation of macrophage polarization through the secretion of interleukin (IL)-10 has been demonstrated. However, the influence of B-1 cells on macrophage phenotype induction by an immunogen that suppress their ability to secrete IL-10 has not been explored. Here, we studied the peritoneal macrophage pattern induced by liposomes comprised of dipalmitoylphosphatidylcholine (DPPC) and cholesterol (Chol) carrying ovalbumin (OVA) (Lp DPPC/OVA), and the involvement of B-1 cells in macrophage polarization. Peritoneal cells from BALB/c, B-1 cells-deficient BALB/xid and C57BL/6 mice immunized with Lp DPPC/OVA and OVA in soluble form (PBS/OVA) were analyzed and stimulated or not in vitro with lipopolysaccharide (LPS). Peritoneal macrophages from BALB/c and C57BL/6 mice immunized with Lp DPPC/OVA showed an M2-like phenotype as evidenced by their high arginase activity without LPS stimulation. Upon stimulation, these macrophages were reprogrammable toward the M1 phenotype with the upregulation of nitric oxide (NO) and a decrease in IL-10 secretion. In addition, high IFN-γ levels were detected in the culture supernatant of peritoneal cells from BALB/c and C57BL/6 mice immunized with Lp DPPC/OVA. Nevertheless, still high levels of arginase activity and undetectable levels of IL-12 were found, indicating that the switch to a classical activation state was not complete. In the peritoneal cells from liposomes-immunized BALB/xid mice, levels of arginase activity, NO, and IL-6 were below those from wild type animals, but the last two products were restored upon adoptive transfer of B-1 cells, together with an increase in IFN-γ secretion. Summarizing, we have demonstrated that Lp DPPC/OVA induce an M2-like pattern in peritoneal macrophages reprogrammable to M1 phenotype after LPS stimulation, with the involvement of B-1 cells.     

Role of macrophages in serum colony-stimulating factor induction by Lactobacillus casei in mice.

Heat-killed Lactobacillus casei YIT9018 (LC9018), when injected intravenously into mice at a dose of 4 to 40 mg/kg, induced the production of serum colony-stimulating factor (CSF). Since this induction was observed in both C3H/HeJ and C3H/HeN mice, LC9018 was considered to act differently from lipopolysaccharide. The amount of serum CSF induced by LC9018 in nude mice and whole-body-X-ray-irradiated mice was similar to that in control mice, but the induction of serum CSF was suppressed by the previous administration of carrageenan, indicating that macrophages, but not T cells, were responsible for serum CSF induction by LC9018. To determine whether macrophages themselves produce CSF or help other cells produce CSF in response to LC9018, we prepared adherent cells from the peritoneal cavity of normal mice and examined CSF activity in their conditioned media. Peritoneal adherent cells did not produce CSF without LC9018, but when cultivated with 1 mg of LC9018 per ml, they produced CSF at the same time that serum CSF was induced after the intravenous administration of LC9018. Additionally, in vitro-induced CSF formed macrophage, granulocyte, and mixed colonies, as serum CSF did. CSF production by peritoneal adherent cells was completely inhibited by cycloheximide (50 micrograms/ml), and neither the elimination of T cells from the peritoneal adherent cells by treating them with anti-Thy-1.2 antibody plus complement nor the addition of T cells affected CSF production. These results suggest that heat-killed LC9018 induces serum CSF in mice via direct stimulation of macrophages to produce CSF de novo.     

Activation of jird (Meriones unguiculatus) macrophages by the filarial parasite Brugia pahangi

Peritoneal macrophages from Mongolian jirds (Meriones unguiculatus) with either lymphatic or intraperitoneal infections of Brugia pahangi were studied to determine the effects of infection on macrophage function and morphology. Macrophages were collected at 40, 90, 140, and 200 days after inoculation of infective third-stage larvae and assayed for phagocytic and bactericidal activity by the acridine orange method and for morphological changes by light and electron microscopy. Significant increases in phagocytic and microbicidal activity (P less than or equal to 0.01) were observed in peritoneal macrophages collected from jirds with intraperitoneal infections when compared with peritoneal macrophages from jirds with lymphatic infections and resident peritoneal macrophages from normal, noninfected jirds. Morphological changes in peritoneal macrophages from jirds with intraperitoneal infections were similar to those found in thioglycolate-elicited macrophage populations. Granuloma formation was also observed in the peritoneal cavities of intraperitoneally infected jirds. The peritoneal cavity may serve as a model to study cell-worm interactions in filarial nematode infections.     

Macrophage Heterogeneity in Thromboplastin Response

The procoagulant activities of non-elicited mouse monocytes/macrophages from four anatomical localizations were compared. These cell populations were further examined for their ability to increase their procoagulant activity on exposure to endotoxin or phytohaemagglutinin (PHA). Peritoneal macrophages exhibited the highest basal procoagulant activity. Their activity was further enhanced by stimulation with endotoxin and PHA, but marked strain differences were noted. This procoagulant has been identified as tissue thromboplastin. Isolated adherent spleen cells, peripheral blood monocytes or lung alveolar macrophages had a low basal procoagulant activity that did not increase on exposure to PHA or endotoxin. The identity of the weak procoagulant in these cells is uncertain. The presence of lymphocytes in the macrophage cultures (4:1 ratio) enhanced slightly (1.3 to 1.5-fold) the response of peritoneal macrophages to endotoxin or PHA but did not significantly influence the procoagulant activity of the other macrophage subpopulations under the conditions tested. These results demonstrate heterogeneity among different macrophage subpopulations with regard to cellular procoagulant expression.     

Increased matrix metalloproteinase-9 activity in human ovarian cancer cells cultured with conditioned medium from human peritoneal tissue

Ovarian cancer cells disseminate by attachment to the peritoneal mesothelial cell surface of the abdominal cavity. We therefore investigated the influence of conditioned medium (CM) from human peritoneal tissues and mesothelial cells on the secretion of matrix metalloproteinases (MMPs) by ovarian cancer cells. The molecular weights of MMPs stimulating factors derived from human peritoneal tissues and mesothelial cells were estimated using microconcentrators with various cut-off membranes. Human peritoneal tissues were obtained from 12 surgical patients, and mesothelial cells were isolated from three peritoneal specimens. Exposure to CM from peritoneal tissue caused a concentration-dependent increase of the MMP-2 and MMP-9 bands in CM from NOM1 ovarian cancer cells, as shown by zymography. There was a significant difference in the increase of MMP-2 and MMP-9 (2.46-fold and 7.14-fold, respectively, at 0.4mg/ml protein; P < 0.005). CM from mesothelial cells also significantly increased the secretion of MMP-9 by NOM1 cells. The molecular size of possible MMP-9-stimulating factors secreted by peritoneal tissues and mesothelial cells was above M 100000. Further, CM of peritoneal tissues and mesothelial cells also induced the invasiveness of NOM1 cells. These findings suggest that mesothelial cells may secrete some factors which predominantly induce the MMP-9 production and increase invading cell numbers.     

Alveolar macrophages. II. Inhibition of lymphocyte proliferation by purified macrophages from rat lung.

Macrophages were prepared from the lung, peritoneal cavity and blood of normal, unstimulated rats from a number of strains. The macrophages were purified by adherence, and characterized via surface markers, enzyme activity and phagocytic capacity, and subsequently tested for activity in cultures of mitogen-stimulated syngeneic lymphocytes. Peritoneal macrophages and blood monocytes were mildly stimulatory, or ineffective in modulating mitogen-induced DNA synthesis; peritoneal macrophages reconstituted the blastogenic responses of macrophage-depleted lymph node cell cultures to normal limits. In contrast, alveolar macrophages were markedly inhibitory to lymphocyte proliferation; in some instances inhibitory activity was demonstrable when added alveolar macrophages comprised only 0.04% of the total cells in culture. Lymphocyte proliferation induced by T-cell mitogens was more susceptible to this inhibition than was proliferation induced by the B-cell mitogen LPS. Alveolar macrophages recovered from SPF rats, while less in number, exhibited comparable inhibitory activity. These results form part of an emerging picture picture of the normal alveolar macrophage as a potential 'suppressor' of T-cell activity in the lung.     

Macrophages and Recently Identified Forms of Cell Death

Recent advances in cell death biology have uncovered an ever increasing range of cell death forms. Macrophages have a bidirectional relationship with cell death that modulates the immune response. Thus, macrophages engulf apoptotic cells and secrete cytokines that may promote cell death in parenchymal cells. Furthermore, the presence of apoptotic or necrotic dead cells in the microenvironment elicits differential macrophage responses. Apoptotic cells elicit anti-inflammatory responses in macrophages. By contrast macrophages may undergo a proinflammatory form of cell death (pyroptosis) in response to damage-associated molecular patterns (DAMPs) released from necrotic cells and also in response to pathogen-associated molecular patterns (PAMPs). Pyroptosis is a recently identified form of cell death that occurs predominantly in subsets of inflammatory macrophages and is associated to the release of interleukin-1β (IL-1β) and IL-18. Deregulation of these processes may result in disease. Thus, failure of macrophages to engulf apoptotic cells may be a source of autoantigens in autoimmune diseases, excessive macrophage release of proapoptotic factors or sterile pyroptosis may contribute to tissue injury and failure of pathogen-induced pyroptosis may contribute to pathogen survival. Ongoing research is exploring the therapeutic opportunities resulting this new knowledge.     

Human peritoneal mesothelial cell transformation into myofibroblasts in response to TGF-ß1 in vitro

Peritoneal dissemination is one of the leading causes of death in gastric cancer patients. The interaction between carcinoma cells and the peritoneal lining may play a key role in tumor peritoneal dissemination. Human peritoneal mesothelial cells are a monolayer of squamous epithelial cells covering the peritoneal cavity and forming serosal membranes. The precise role of mesothelial cells in the peritoneal dissemination of gastric cancer remains to be identified. Expression of TGF-?1, a cytokine known for its capacity to induce proliferative and transformative changes in cells, has been correlated with peritoneal metastasis and TNM stages of gastric cancer. High levels of TGF-?1 in the subperitoneal milieu may play a key role in the transition of normal mesothelial cells to myofibroblasts. Here, we demonstrate that mesothelial cells activated by TGF-?1 undergo epithelial-mesenchymal transition (EMT) and that the transition of mesothelial cells to myofibroblasts is dependent on Smad2 signaling. EMT of mesothelial cells was marked by up-regulation of α-smooth muscle actin and vimentin expression. Cytokeratin and E-cadherin expression decreased over time in transformed mesothelial cells. Knockdown of Smad2 gene by siRNA silencing significantly suppressed the transition of mesothelial cells to myofibroblasts. We conclude that when exposed to TGF-?1 mesothelial cells undergo EMT which involves Smad2 signaling. Furthermore, mesothelial cells may be the possible source of myofibroblasts in peritoneal fibrosis and provide a favorable environment for the dissemination of gastric cancer.     

The peritoneum: healing,immunity, and diseases

The peritoneum defines a confined microenvironment, which is stable under normal conditions, but is exposed to the damaging effect of infections, surgical injuries, and other neoplastic and non‐neoplastic events. Its response to damage includes the recruitment, proliferation, and activation of a variety of haematopoietic and stromal cells. In physiological conditions, effective responses to injuries are organized; inflammatory triggers are eliminated; inflammation quickly abates; and the normal tissue architecture is restored. However, if inflammatory triggers are not cleared, fibrosis or scarring occurs and impaired tissue function ultimately leads to organ failure. Autoimmune serositis is characterized by the persistence of self‐antigens and a relapsing clinical pattern. Peritoneal carcinomatosis and endometriosis are characterized by the persistence of cancer cells or ectopic endometrial cells in the peritoneal cavity. Some of the molecular signals orchestrating the recruitment of inflammatory cells in the peritoneum have been identified in the last few years. Alternative activation of peritoneal macrophages was shown to guide angiogenesis and fibrosis, and could represent a novel target for molecular intervention. This review summarizes current knowledge of the alterations to the immune response in the peritoneal environment, highlighting the ambiguous role played by persistently activated reparative macrophages in the pathogenesis of common human diseases. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Akt2 is required for macrophage chemotaxis

Tumor‐associated macrophages play an important role in tumorigenesis and metastasis. Trafficking of macrophages to the proximity of tumors is mediated by CSF‐1, a growth factor. In this study, we investigated the role of PKB/Akt in CSF‐1‐induced macrophage migration. Disruption of Akt2 expression by small interference RNA impaired chemotaxis of both THP‐1 cells and mouse peritoneal macrophages. Phosphorylation of PKCζ, an essential component in chemotaxis signaling pathway, was reduced. LIMK/Cofilin, downstream of PKCζ, regulated cytoskeleton rearrangement during cell migration. Disruption of Akt2 expression inhibited CSF‐1‐induced LIMK/Cofilin phosphorylation, which contributed to defects in actin polymerization and chemotaxis. Furthermore, MCP‐1, a chemokine, ‐induced macrophage chemotaxis was also impaired. Taken together, our results demonstrated that Akt2 plays an essential role in both CSF‐1‐ and chemokine‐induced chemotaxis of macrophages.     

Immunoregulation by macrophages. III. Prostaglandin E suppresses lymphocyte activation but not macrophage effector function during Salmonella enteritidis infection

Peritoneal macrophages obtained during primary or secondary infection with Salmonella enteritidis differ in the proportions of subpopulations with the capacity to secrete prostaglandin E (PGE) and interleukin 1 (IL1) and have bactericidal and tumoricidal activities in vitro. Using indomethacin in vivo and PGE in vitro we have studied the regulation of subpopulations of lymphocytes and macrophages by PGE during the inflammatory reaction. Indomethacin treatment promoted clearance of the Salmonella and a 50-90% increase in macrophages recovered from the peritoneal cavity in both primary and secondary infected animals. Whilst blocking the capacity of macrophages to secrete PGE in vitro the indomethacin treatment did not alter their bactericidal (or tumoricidal) activity nor their cyclic AMP response to PGE2. A major effect of indomethacin in vivo and of PGE2 in vitro however, was on the production and expression of IL1 and IL2. Secretion of IL1 by macrophages in vitro was greatly enhanced in indomethacin treated mice and was suppressed in vitro by PGE2. Prostaglandin E2 also inhibited IL1 dependent T-lymphocyte differentiation. IL2 secretion and IL2 dependent blast cell proliferation in vitro and sensitivity of the cells to PGE2 inhibition increased through this sequence of reactions. Lymphocyte populations harvested at intervals during primary or secondary infection differed in their cyclic AMP response to PGE2 and in IL2 secretion in vitro. This may be related to changes in the proportions of lymphocyte subsets having Lyt 1+ markers. We conclude that peritoneal macrophages from Salmonella infected mice differ in their capacity to secrete PGE and IL1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Macrophages: Supportive cells for tissue repair and regeneration

Macrophages, and more broadly inflammation, have been considered for a long time as bad markers of tissue homeostasis. However, if it is indisputable that macrophages are associated with many diseases in a deleterious way, new roles have emerged, showing beneficial properties of macrophages during tissue repair and regeneration. This discrepancy is likely due to the high plasticity of macrophages, which may exhibit a wide range of phenotypes and functions depending on their environment. Therefore, regardless of their role in immunity, macrophages play a myriad of roles in the maintenance and recovery of tissue homeostasis. They take a major part in the resolution of inflammation. They also exert various effects of parenchymal cells, including stem and progenitor cell, of which they regulate the fate. In the present review, few examples from various tissues are presented to illustrate that, beyond their specific properties in a given tissue, common features have been described that sustain a role of macrophages in the recovery and maintenance of tissue homeostasis.     

Peritoneal Cavity is a Route for Gut‐Derived Microbial Signals to Promote Autoimmunity in Non‐Obese Diabetic Mice

Macrophages play a crucial role in innate immune reactions, and peritoneal macrophages (PMs) guard the sterility of this compartment mainly against microbial threat from the gut. Type 1 diabetes (T1D) is an autoimmune disease in which gut microbiota and gut immune system appear to contribute to disease pathogenesis. We have recently reported elevated free radical production and increased permeability of gut epithelium in non‐obese diabetic (NOD) mice. Impaired barrier function could lead to bacterial leakage to the peritoneal cavity. To explore the consequences of impaired gut barrier function on extra‐intestinal immune regulation, we characterized peritoneal lavage cells from young newly weaned NOD mice. We detected a rapid increase in the number of macrophages 1–2 weeks after weaning in NOD mice compared to C57BL/6 and BALB/c mice. Interestingly, this increase in macrophages was abrogated in NOD mice that were fed an antidiabetogenic diet (ProSobee), which improves gut barrier function. Macrophages in young (5‐week‐old) NOD mice displayed a poor TNF‐α cytokine response to LPS stimulation and high expression of interleukin‐1receptor‐associated kinase‐M (IRAK‐M), indicating prior in vivo exposure to TLR‐4 ligand(s). Furthermore, injection of LPS intraperitoneally increased T cell CD69 expression in pancreatic lymph node (PaLN), suggestive of T cell activation. Leakage of bacterial components such as endotoxins into the peritoneal cavity may contribute to auto‐reactive T cell activation in the PaLN.     

Role of prostaglandin E and interferon in secretion of colony-stimulating factor by murine macrophages after in vitro treatment with biological response modifiers

We have evaluated the possible role of biological response modifiers (BRMs) in myelopoiesis by investigating BRM modulated secretion of hematopoietic growth factors and inhibitors. Here, we report the evidence of augmented secretion of granulocyte and/or macrophage colony stimulating factors (CSF) by murine resident peritoneal macrophages after in vitro incubation with murine interferons (alpha, beta-mIFN; beta-mIFN; gamma-mIFN), poly ICLC (polyriboinosinic-polycytidylic acid poly-L-lysine), BM 41.332 (2-cyano-1-[(2-methoxy-6-methyl-pyridin-3yl)-methyl]-aziridine) and lipopolysaccharide (LPS). The secretion of CSF appears to be independent of the ability of the BRMs to induce IFN, as shown by the use of neutralizing antibodies against mIFN. The antiproliferative effects of IFN also did not block the BRM induced effects of CSF. The combination of alpha, beta-mIFN and poly ICLC or LPS and poly ICLC at suboptimal concentrations resulted in additive, but not synergistic effects on CSF secretion by macrophages. Histological examination of the colonies induced indicated the presence of two types of CSF, namely CSF1 and CSF3, which give rise to pure macrophage and granulocyte colonies respectively. In parallel to their effect on CSF secretion, these BRMs also caused a considerable increase in secretion of prostaglandins of the E series (PGE) by macrophages. However, the production of PGE did not interfere or influence CSF secretion, since the inhibition of the enzyme cyclooxygenase with indomethacin (10(-7) molar) 3 h before stimulation with poly ICLC, alpha, beta-mIFN, or LPS, inhibited the secretion of PGE by macrophages without affecting the secretion of CSF. Macrophages, stimulated by one of the active BRMs for 24 h, could not be restimulated by any of these agents to again secrete significant amounts of CSF or PGE, even after a 2 day resting phase. Other drugs tested (diethyldithiocarbamate, maleic anhydride divinyl ether, azimexone) failed to stimulate the in vitro secretion of significant amounts of CSF and PGE. The results presented here indicate that several BRMs can be utilized to stimulate macrophages to secrete the myelopoietic growth factor CSF, thus supporting the concept that these BRMs might be of value in reconstituting or promoting impaired granulocyte and monocyte/macrophage function.     

Carcinoma‐associated fibroblasts derive from mesothelial cells via mesothelial‐to‐mesenchymal transition in peritoneal metastasis

Peritoneal dissemination is a frequent metastatic route for cancers of the ovary and gastrointestinal tract. Tumour cells metastasize by attaching to and invading through the mesothelial cell (MC) monolayer that lines the peritoneal cavity. Metastases are influenced by carcinoma‐associated fibroblasts (CAFs), a cell population that derives from different sources. Hence, we investigated whether MCs, through mesothelial–mesenchymal transition (MMT), were a source of CAFs during peritoneal carcinomatosis and whether MMT affected the adhesion and invasion of tumour cells. Biopsies from patients with peritoneal dissemination revealed the presence of myofibroblasts expressing mesothelial markers in the proximity of carcinoma implants. Prominent new vessel formation was observed in the peritoneal areas harbouring tumour cells when compared with tumour‐free regions. The use of a mouse model of peritoneal dissemination confirmed the myofibroblast conversion of MCs and the increase in angiogenesis at places of tumour implants. Treatment of omentum MCs with conditioned media from carcinoma cell cultures resulted in phenotype changes reminiscent of MMT. Adhesion experiments demonstrated that MMT enhanced the binding of cancer cells to MCs in a β1‐integrin‐dependent manner. Scanning electron microscopy imaging showed that the enhanced adhesion was mostly due to increased cell–cell interaction and not to a mere matrix exposure. Invasion assays suggested a reciprocal stimulation of the invasive capacity of tumour cells and MCs. Our results demonstrate that CAFs can derive from mesothelial cells during peritoneal metastasis. We suggest that MMT renders the peritoneum more receptive for tumour cell attachment/invasion and contributes to secondary tumour growth by promoting its vascularization. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.