Nurse-like cells in rheumatoid arthritis: Formation of survival niches cooperating between the cell types

Abstract

Nurse-like cells (NLCs) established from bone marrow and synovial tissue of rheumatoid arthritis (RA) patients were found to promote maturation and differentiation of B lineage cells as well as T cells. In co-culture of RA-NLCs and B cells, tight physical interactions (pseudoemperipolesis) developed, which resulted in activation of both cell types. RA-NLCs also supported myeloid cell maturation, promoting their differentiation into tartrate-resistant acid phosphatase-positive mononuclear cells, which are precursor cells of osteoclasts. In RA synovial tissue, the characteristic dendritic-shaped cells (the DCs) were electron microscopically found to form direct physical interactions with adjacent plasma cells (PCs) suspecting to be pseudoemperipolesis. The numbers of PCs accumulating in various areas tended to correlate with the numbers of the DCs, which appeared to have RA-NLC functions forming survival niches for PCs. Immunohistochemical staining analysis indicated that CD14+ cells including the DCs formed survival niches for CD138+ PCs by RA-NLC functions. Quantitative dual immunofluorescence staining studies of these areas indicated that the majority of CD14+ cells were of myeloid lineage. These survival niches promoted by RA-NLCs appear to play important roles in supporting immunological functions in RA bone marrow and synovial tissues.     

A role for niches in hematopoietic cell development

Stem cells reside in a physical niche, a particular microenvironment. The organization of cellular niches has been shown to play a key role in regulating normal stem cell differentiation, maintenance and regeneration. Hematopoietic stem cells (HSC) emerge at distinct allocation territories during ontogenesis, notably the aorto-gonadal region, the fetal liver. Adult HSC expand and differentiate exclusively in the bone marrow (BM). They can be mobilized into the blood stream. This implies that stem cells are not autonomous units of development; rather, tissue specific niches control their destiny. Interaction of HSCs with their stem cell niches is critical for adult hematopoiesis in the BM. A niche is composed of stromal cells, which either through direct cell-to-cell contact or via release of soluble factors maintain the typical features of stem cells, mainly stem cell quiescence, maintenance or expansion. HSCs are keeping the balance of the quiescence and the self-renewal in the stem cell niche, and are maintaining long-term hematopoiesis. Therefore, an understanding of cellular and chemical architecture of the stem cell niche is vital in understanding stem cell behavior. This review summarizes the recent developments in our understanding of the stem cell niche with particular focus on the HSC niche.     

肺转移瘤的转移前微环境与转移微环境

一个多世纪前Paget就肿瘤器官特异性转移现象提出了“种子与土壤”学说。时下研究热点集中在一些特殊因子介导的靶器官环境改造,肿瘤细胞归巢行为。有动物实验证实肺转移瘤形成前,肺部已发生大量炎症因子聚集。宿主靶器官的改变影响转移瘤形成的每一个步骤。BethanPsaila与DavidLyden针对这一土壤变化过程提出转移前微环境（pre-metastaticniche）及转移微环境（metastaticniche）假说,指出土壤的变化是转移瘤形成的保障。该假说提出后迅速引起肿瘤研究界轰动。研究这一系列细胞分子生物学的改变,有助于阐明肿瘤转移这一复杂的过程,为转移干预带来新的思路。     

eIF4A controls germline stem cell self-renewal by directly inhibiting BAM function in the Drosophila ovary

Stem cell self-renewal is controlled by concerted actions of extrinsic niche signals and intrinsic factors in a variety of systems. Drosophila ovarian germline stem cells (GSCs) have been one of the most productive systems for identifying the factors controlling self-renewal. The differentiation factor BAM is necessary and sufficient for GSC differentiation, but it still remains expressed in GSCs at low levels. However, it is unclear how its function is repressed in GSCs to maintain self-renewal. Here, we report the identification of the translation initiation factor eIF4A for its essential role in self-renewal by directly inactivating BAM function. eIF4A can physically interact with BAM in Drosophila S2 cells and yeast cells. eIF4A exhibits dosage-specific interactions with bam in the regulation of GSC differentiation. It is required intrinsically for controlling GSC self-renewal and proliferation but not survival. In addition, it is required for maintaining E-cadherin expression but not BMP signaling activity. Furthermore, BAM and BGCN together repress translation of E-cadherin through its 3′ UTR in S2 cells. Therefore, we propose that BAM functions as a translation repressor by interfering with translation initiation and eIF4A maintains self-renewal by inhibiting BAM function and promoting E-cadherin expression.     

Cellular basis of cancer metastasis: A review of fundamentals and new advances

This review provides an introduction to fundamentals and new advances in cancer metastasis for general readers. The first segment includes topics such as cell adhesion, cell migration, proteases, inflammation, coagulation and site selection in metastasis. Then follows a discussion of an interesting report by Kaplan et al. [VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 2005;438:820-7] that provides evidence for a role of VEGFR1+bone marrow cells in preparing pre-metastatic niches in specific organs that host the arrival and growth of metastatic cancer cells. The therapeutic implications of this study are explored.     

P2Y2R activation by nucleotides released from the highly metastatic breast cancer cell contributes to pre-metastatic niche formation by mediating lysyl oxidase secretion,collagen crosslinking,and monocyte recruitment

Tumor microenvironmental hypoxia induces hypoxia inducible factor-1α (HIF-1α) overexpression, leading to the release of lysyl oxidase (LOX), which crosslinks collagen at distant sites to facilitate environmental changes that allow cancer cells to easily metastasize. Our previous study showed that activation of the P2Y₂ receptor (P2Y₂R) by ATP released from MDA-MB-231 cells increased MDA-MB-231 cell invasion through endothelial cells. Therefore, in this study, we investigated the role of P2Y₂R in breast cancer cell metastasis to distant sites. ATP or UTP released from hypoxia-treated MDA-MB-231 cells induced HIF-1α expression and LOX secretion by the activation of P2Y₂R, and this phenomenon was significantly reduced in P2Y₂R-depleted MDA-MB-231 cells. Furthermore, P2Y₂R-mediated LOX release induced collagen crosslinking in an in vitro model. Finally, nude mice injected with MDA-MB-231 cells showed high levels of LOX secretion, crosslinked collagen and CD11b⁺ BMDC recruitment in the lung; however, mice that were injected with P2Y₂R-depleted MDA-MB-231 cells did not exhibit these changes. These results demonstrate that P2Y₂R plays an important role in activation of the HIF-1α–LOX axis, the induction of collagen crosslinking and the recruitment of CD11b⁺ BMDCs. Furthermore, P2Y₂R activation by nucleotides recruits THP-1 monocytes, resulting in primary tumor progression and pre-metastatic niche formation.