Abstract

The integrins are receptors that regulate interaction between epithelial cells and the extracellular matrix. Previous studies have shown that a reduction in the expression of the alpha2beta1, alpha3beta1, alpha6beta1, alpha(v)beta1 and alpha(v)beta5 integrins in primary breast cancer is associated with positive nodal status. In order to assess the functional significance of altered integrin expression, primary breast cancer cells were derived from individual patients with known tumour characteristics using immunomagnetic separation. Purified human fibronectin, vitronectin, laminin and type IV collagen were used to represent the principal extracellular matrix proteins in an in vitro adhesion assay. Primary breast cancer cells from lymph node-positive patients were significantly less adhesive to each of the matrix proteins studied (P<0.001, Mann-Whitney U-test). Matrix adhesion of primary breast cancer cells from node-negative patients was inhibited by appropriate integrin monoclonal antibodies (P<0.001, paired Wilcoxon test). Adhesion to fibronectin, vitronectin and laminin, but not type IV collagen, was influenced by the inhibitor arginine-glycine-aspartate, suggesting that breast cancer cell recognition of collagen IV is mediated through alternative epitopes. Weak matrix adhesion correlated with loss of integrin expression in tissue sections from corresponding patients assessed using immunohistochemistry. This study demonstrates a link between altered integrin expression and function in primary breast cancers predisposed to metastasize.

Highlights

  • Owing to limitations on cell quantity required by these experiments, the actual number of patients studied for each matrix protein were: fibronectin n = 40 [19 lymph node-negative (LN-) and 21 lymph node-positive (LN+)], vitronectin n = 40 (20 LN, 20 LN +), laminin n = 39 (20 LN, 19 LN +) and type IV collagen n = 39 (19 LN, 20 LN+)

  • This study demonstrates for the first time a relationship between integrin receptor expression and function in patient-derived human breast cancer cells

  • In cancer, reduced adhesion may result in less sticky tumour cells able to move unhindered in the extracellular matrix, predisposed to metastasize

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Summary

Objectives

The aim of this study was to evaluate cell-matrix adhesion in tumour progression

Methods
Results
Discussion
Conclusion

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