Novel interaction of MUC4 and galectin: Potential pathobiological implications for metastasis in lethal pancreatic cancer

Shantibhusan Senapati, Pallavi Chaturvedi, William G. Chaney, Subhankar Chakraborty, Vinayaga S. Gnanapragassam, Aaron R. Sasson, Surinder K. Batra

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Purpose: Several studies have reported aberrant expression of MUC4 in pancreatic cancer (PC), which is associated with tumorigenicity and metastasis. Mechanisms through which MUC4 promote metastasis of PC cells to distant organs are poorly defined. Experimental Design: Identification of MUC4-galectin-3 interaction and its effect on the adhesion of cancer cells to endothelial cells were done by immunoprecipitation and cell-cell adhesion assays, respectively. Serum galectin-3 level for normal and PC patients were evaluated through ELISA. Results: In the present study, we have provided clinical evidence that the level of galectin-3 is significantly elevated in the sera of PC patients with metastatic disease compared with patients without metastasis (P = 0.04) and healthy controls (P = 0.00001). Importantly, for the first time, we demonstrate that MUC4 present on the surface of circulating PC cells plays a significant role in the transient and reversible attachment (docking) of circulating tumor cells to the surface of endothelial cells. Further, exogenous galectin-3 at concentrations similar to that found in the sera of PC patients interacts with MUC4 via surface glycans such as T antigens, which results in the clustering of MUC4 on the cell surface and a stronger attachment (locking) of circulating tumor cells to the endothelium. Conclusions: Altogether, these findings suggest that PC cell-associated MUC4 helps in the docking of tumor cells on the endothelial surface. During cancer progression, MUC4-galectin-3 interaction-mediated clustering of MUC4 may expose the surface adhesion molecules, which in turn promotes a stronger attachment (locking) of tumor cells to the endothelial surface.

Original languageEnglish (US)
Pages (from-to)267-274
Number of pages8
JournalClinical Cancer Research
Volume17
Issue number2
DOIs
StatePublished - Jan 15 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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