Enhanced Adhesion of Stromal Cells to Invasive Cancer Cells Regulated by Cadherin 11

Cancer-associated fibroblasts (CAEs) are known to promote tumor growth and metastasis; however their differential accumulation in invasive and noninvasive tumors is not fully understood. We hypothesized that differences in cell adhesion may contribute to this phenomenon. To test this, we analyzed the adhesion of CAF-precursor fibroblasts and mesenchymal stem cells to invasive and noninvasive cancers originating from the the breast, ovaries, and prostate. In all cases, stromal cells preferentially adhered to more invasive cancer cells. Modulating integrin and cadherin binding affinities with calcium chelation revealed that adhesion was independent of integrin activity but required cadherin function. Invasive cancer cells had increased expression of mesenchymal markers cadherin 2 and 11 that localized with stromal,cell cadherin 11, suggesting that these molecules are involved in stromal cell engraftment. Blockade of cadherin 11 on stromal cells inhibited adhesion and may serve as a target for metastatic disease.