Laminin and its cognate receptors in cholangiocarcinoma progression

        Cholangiocarcinoma (CCA), a malignant epithelial cancer arising in bile ducts, has not only poor prognosis and therapeutic outcomes, but also growing incidence rate with the highest prevalence in northeastern Thailand. Several lines of evidences indicate that the prominent remodeling of extracellular matrix (ECM) in cancer nurtures tumor development. Due to the highly desmoplastic nature of CCA, it urges a further understanding in CCA cell-matrix interaction. Therefore, the aim of this study was to clarify the involvement of ECM and their receptor interaction in harnessing CCA progression. Here, the ECM proteins named laminin was identified as the most potent attractant for CCA cell migration, a critical property of metastatic cells. Its receptors, integrin β4 (ITGB4) and 37/ 67-kDa laminin receptor (LAMR), were shown to be upregulated in CCA cell lines. Overexpression of laminin and its receptor, ITGB4, was also demonstrated in CCA tissues with the correlation with lymphatic invasion. Besides, the existence of ITGB4 was also associated with patients’ short survival time. In addition, we revealed that communication between laminin and its receptors was crucial for migration of CCA cells. Given the data, our findings highlight the role of ECM protein and its cognate receptors in inducing CCA migration as well as the potential usage of ITGB4 as a diagnostic and prognostic biomarker for CCA.

Reference

Islam K, Thummarati P, Kaewkong P, Sripa B, Suthiphongchai T. Role of laminin and cognate receptors in cholangiocarcinoma cell migration. Cell adhesion & migration. 2021;15(1):152-65. https://doi.org/10.1080/19336918.2021.1924422