Laminin mediates tethering and spreading of colon cancer cells in physiological shear flow

Abstract

Summary Under the physiological shear condition, cultured colon cancer cells bound to laminin (LM), but not to fibronectin or vitronectin. Most of the tethered cells did not roll, but arrested immediately and spread within 10-30 min on LM under the continuous presence of shear flow. The tethering of Colo201 was partially inhibited by monoclonal antibodies (mAbs) to α6 integrin and a combination of mAbs to β1 and β4 integrins, but not by mAb to 67KD laminin receptor. Some Colo201 cells still tethered at 4°C. This suggests that α6β1 and α6β4 integrins participate in Colo201 tethering on LM, although other non-integrin molecules play roles. In contrast, the spread of Colo201 was effectively inhibited by the mAbs to integrin α2, α6 and β1 chains. The effect of anti-α2 plus anti-α6 mAbs was almost equal to anti-β1, suggesting that Colo201 cells mainly use α2β1 and α6β1 integrins for spreading on LM. When the cells were perfused on subconfluent endothelial cells (HUVEC) cultured on LM, they did not tether on HUVEC but did on coated LM exposed at intercellular gap area. Immunohistochemistry revealed that LM abundantly existed in the cytosol of human portal and hepatic vein endothelial cells. These data suggest that LM can mediate from tethering to spreading of colon cancer cells under the blood flow and plays an essential role in haematogeneous metastasis.

Organ-Specific Metastatic Tumor Cell Adhesion and Extravasation of Colon Carcinoma Cells with Different Metastatic Potential

“…Furthermore, biochemical interactions between adhesion molecules and their ligands during tumor cell adhesion within circulatory systems appear to be influenced by biophysical factors, such as shear stress caused by fluid flow, and cellular and soluble components of the circulating fluid. [15][16][17] Intravital microscopy technologies have been recently used to investigate metastatic tumor cell adhesion within host organ microcirculation, such as in liver and lung. 10 -14 In these studies contradictory results were reported regarding the type of entrapment (mechanical entrapment 10 -12 versus active cell adhesion 14,18 ) and the requirement of invasion into host organ parenchyma (invasion 10,11,13,18 versus intravascular proliferation 14 ).…”

Cross-Talk between Alternatively Spliced UGT1A Isoforms and Colon Cancer Cell Metabolism

“…Strongly adherent cells may increase their migration capacity through a decrease of their adhesion to extracellular matrix. While subtle, we observed a differential adhesion capacity of KD cells, namely for laminin, a non-collagenous extracellular matrix critical in colon cancer and linked to tumor angiogenesis, epithelial-mesenchymal transition and metastasis (Guess et al, 2009;Kitayama et al, 1999;Simon-Assmann et al, 2011). Accordingly, this observation may partially explain the differential migration phenotype between low and high UGT1A_i2 expressing cell lines.…”

CD49f-positive cell population efficiently enriches colon cancer-initiating cells

“…In our previous report (31) CD49f, also known as integrin α6 (ITGA6), is a major laminin receptor and mediates cell adhesion (16,18,19,21). In colon cancer, expression of CD49f has been reported to be associated with tumor cell invasion and metastasis via integrin-mediated cell signaling and adhesion to the extracellular matrix (16,18,19,21). CSCs in various cancers show high metastatic potency (12)(13)(14)(15).…”

“…We also assessed CD49f and CXCR4 expression, because CD49f was reported as a marker of breast (34), prostate (35) and glioblastoma (36) CSCs and CXCR4 was reported to be a marker of pancreas CSCs (12). CD49f and CXCR4 is also known to deeply associate with cancer metastasis (12,(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). The expression of CD44 was drastically reduced by NaBT treatment (rate of change, -99.2% in HT29 and -97.2% in Caco2; average, -98.2%).…”

“…The assessment of markers for cancer cell metastasis might also be important for the study of CSC in CRC. CD49f, also known as integrin α6 (ITGA6), is reportedly associated with tumor cell invasion and metastasis in CRC (16)(17)(18)(19)(20)(21). The chemokine receptor CXCR4 plays a critical role in cancer cell metastasis via stromal interaction and hypoxia-related pathways (12,(22)(23)(24)(25)(26).…”