title: Mechano-transduction mediated secretion and uptake of galectin-3 in breast carcinoma cells: implications in the extracellular functions of the lectin.
abstract: In the following experiments, we sought to understand the triggering mechanism which propels galectin-3 to be secreted into the extracellular compartment from its intracellular stores in breast carcinoma cells. We also wanted to analyze in greater details the role of galectin-3 in cellular adhesion and spreading. To do this, we made use of two pairs of breast carcinoma cell lines where one of the pair has high expression of galectin-3 and the other low expression of the lectin. We determined that galectin-3 secreted into the conditioned medium of sub-confluent and spread cells in culture was quite low, almost negligible. However, once the cells were detached and rounded up, a mechano-sensing mechanism triggered the rapid secretion of galectin-3 into the conditioned medium. The secretion was constitutive as long as the cells remained detached. Galectin-3 was shown to be actively taken up from the conditioned medium by spreading cells. The cells which express and secrete high levels of galectin-3 adhered and spread much faster on plastic than those with reduced expression. The uptake of galectin-3 according to our data was important in cell spreading because if this process was compromised significantly, cells failed to spread. The data suggested that galectin-3 uptake modulates the adhesion plaques in that cells which express high levels of galectin-3 have thin-dot like plaques that may be suited for rapid adhesion and spreading while cells in which galectin-3 expression is reduced or knocked-down, have thick and elongated plaques which may be suited for a firmer adhesion to the substratum. Recombinant galectin-3 added exogenously reduced the thickness of the adhesion plaques of tumor cells with reduced galectin-3 expression. Taken together, the present data suggest that galectin-3 once externalized, is a powerful modulator of cellular adhesion and spreading in breast carcinoma cells.
authors.affiliation: Department of Biomedical Sciences, Division of Cancer Biology, Meharry Medical College, Vanderbilt University, Nashville, TN, USA.
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Baptiste
authors.forename: Ashley
authors.initials: A
authors.lastname: James
authors.forename: Margaret
authors.initials: M
authors.lastname: Saria
authors.forename: Josiah
authors.initials: J
authors.lastname: Ochieng
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D005110:Extracellular Space / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000502:physiology*; D021381:Protein Transport / Q000187:drug effects; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: D037502:Galectin 3; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin