Journal
EXPERIMENTAL CELL RESEARCH
Volume 313, Issue 4, Pages 652-664Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2006.11.005
Keywords
galectin-3; secretion; uptake; extracellular; adhesion plaque; mechano-transduction; integrin; breast; carcinoma; growth factor
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Funding
- NCI NIH HHS [U54 CA091408-010006, U54 CA091408, IU54 CA091408] Funding Source: Medline
- NIGMS NIH HHS [S06 GM008037, U54 GM062116, GM62116, S06 GM008037-280072] Funding Source: Medline
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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. (c) 2006 Elsevier Inc. All rights reserved.
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