Matrigel induces L-plastin expression and promotes L-plastin-dependent invasion in human cholangiocarcinoma cells

Abstract

The function of the extracellular matrix (ECM) in the tumor microenvironment is not limited to forming a barrier against tumor invasion. As demonstrated in pathological specimens, cholangiocarcinoma samples exhibit an enrichment of the ECM surrounding the tumor cells. In this study, we examined involvement of the ECM in the regulation of the invasiveness of cholangiocarcinoma cells. The RMCCA1 cholangiocarcinoma cell line was cultured in culture plates either with or without a coating of reconstituted ECM basement membrane preparation (BD Matrigel matrix). In vitro invasion assays were then performed. In addition, the protein expression profile of the cell line was examined using two-dimensional gel electrophoresis and liquid chromatography-tandem mass spectrometry. The proteins expressed and their functional associations with cancer progression were determined. Culturing the RMCCA1 cell line in the BD Matrigel matrix induced cell invasion. Numerous proteins were induced by culturing the RMCCA1 cells in the matrix gel. The expression of L-plastin, an actin-binding protein, was significantly upregulated. The knockdown of L-plastin expression by siRNA silencing significantly suppressed the cellular response to matrix gel-stimulated cancer cell invasion. The ECM promotes the invasiveness of cholangiocarcinoma cells by upregulating L-plastin. These findings suggest the potential exploitation of this mechanism as a means of inhibiting the invasiveness of cholangiocarcinoma cells.

Exosomal Release of L-Plastin by Breast Cancer Cells Facilitates Metastatic Bone Osteolysis

“…Our data are consistent with the previous studies of PRDX4, overexpression of which was identified in many cancer types [53], including breast [54] and prostate [52], [55]. Based on the L-plastin role in tumor cell invasiveness [17], [45], [56], [57], [58], [59], [60], it was proposed to be used as a diagnostic marker [19], [61]; prognostic marker [62]; or a therapeutic target [60], [63], [64]. Our data demonstrate that extracellular L-plastin and PRDX4 have a specific role in stimulating osteoclastogenesis and thus promoting osteolysis during cancer metastasis to bone and suggest that information regarding the expression of these proteins may be particularly useful in cancers with frequently bone metastasis.…”

Effect of the miR‑96‑5p inhibitor and mimic on the migration and invasion of the SW480‑7 colorectal cancer cell line

“…The RMCCA1 cells, a cholangiocarcinoma cell line, cultured with a coating of Matrigel are more invasive than cells maintained in Matrigel-free plates. The protein expression profile indicated that the expression of the actin-binding protein L-plastin is upregulated by Matrigel, and the subsequent loss-of-function study, using siRNA, demonstrated that the knockdown of L-plastin reduces cell invasion induced by Matrigel (44). Vimentin, an intermediate filament protein type, is associated with a high degree of invasiveness (45,46).…”

Targeted deletion of the zebrafish actin-bundling protein L-plastin (lcp1)

“…Conversely, aberrant L-plastin expression is a hallmark of cancer [ 15 ]. Experimental activation of L-plastin can enhance the proliferation, invasiveness and lethality of tumor cells both in vivo and in vitro , whereas suppression can reverse these characteristics [ 16 – 22 ]. Because of its limited expression in normal cells and mechanistic role in many malignancies, L-plastin has been frequently studied as a cancer diagnostic marker [ 23 ], prognostic marker [ 24 ], or therapeutic target [ 25 , 26 ].…”