In vitro modulation of cellular localization of milk fat globule membrane antigens in human breast carcinomas

Alterations in the cellular localization of cell surface components such as the milk fat globule membrane are a common feature of breast carcinomas and relate to the differentiation of a tumour. This study has examined the potential modulation of such components. A group of carcinomas were cultured with and without insulin and/or hydrocortisone and the site of staining for milk fat globule membrane, as detected by the antibodies HMFG 1, HMFG 2, and NCRC 11, was assessed using light microscopic and electron microscopic immunohistochemistry. Modulation of localization, with a shift from cytoplasmic vesicle labelling to submembraneous vesicles/cell surface labelling and intracytoplasmic luminal labelling, was observed in 5 of 14 moderately differentiated and 8 of 11 poorly differentiated carcinomas. Two well differentiated carcinomas continued to show peripheral labelling; three poorly differentiated carcinomas showed no change from cytoplasmic labelling only; and the other carcinomas exhibited heterogeneous localization, making any change difficult to assess. Insulin was required for any change to be observed and it is suggested that this has an effect on the mechanisms for intracellular transport of membrane and secretory proteins.