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The lymphatic endothelial cell (LEC) is an interactive surface for cancer cells. This article aims to explore cancer cell-induced changes of LEC, and study the tumor-lymphatic endothelium interaction. Here, LECs were co-cultured with highly and poorly metastatic tongue cancer cells. The differences in biologic behaviors and gene expression profiles between them were examined. The results showed that LECs induced by highly metastatic cancer cells displayed abnormal biologic behaviors, and could secrete chemokines to promote the migration of cancer cells. Therefore, biologic properties and functional status of LECs in oral tongue squamous cell carcinoma (OTSCC) might be a positive factor in lymphatic dissemination.

Objective: Oral squamous cell carcinoma (OSCC) often spreads from the primary tumor to regional lymph nodes in the early stage. Better understanding of the biology of lymphatic spread of oral cancer cells is important for improving the survival rate of cancer patients., Methods: We established the cell line LNMTca8113 by repeated injections in foot pads of nude mice, which had a much higher lymphatic metastasis rate than its parental cell line Tca8113. Then, we compared the biologic behaviors of cancer cells between them. Moreover, microarray-based expression profiles between them were also compared, and a panel of differential genes was validated using real-time-PCR., Results: In contrast to Tca8113 cells, LNMTca8113 cells were more proliferative and resistant to apoptosis in the absence of serum, and had enhanced ability of inducing capillary-like structures. Moreover, microarray-based expression profiles between them identified 1341 genes involved in cell cycle, cell adhesion, lymphangiogenesis, regulation of apoptosis, and so on. Some genes dedicating to the metastatic potential, including JAM2, TNC, CTSC, LAMB1, VEGFC, HAPLN1, ACPP, GDF9 and FGF11, were upregulated in LNMTca8113 cells., Conclusion: These results suggested that LNMTca8113 and Tca8113 cells were proper models for lymphatic metastasis study because there were differences in biologic behaviors and metastasis-related genes between them. Additionally, the differentially expressed gene profiles in cancer progression may be helpful in exploring therapeutic targets and provide the foundation for further functional validation of these specific candidate genes for OSCC.

Understading functional properties of tumor-derived lymphatic endothelial cells (TLEC) are relevant for blocking lymphatic metastasis. The changes of lymphatic endothelial cells (LEC) cocultured with oral cancer cells in a vitro model were examined. TLEC, in contrast to LEC, were more proliferative and have enhanced ability of lymphangiogenesis and anti-apoptosis. Gene microarrays revealed that 677 unique genes had two-fold or higher change between the two groups. Differential expressions of selected genes were confirmed by real-time PCR. Our results indicate that TLEC display abnormal characteristics and are distinct at the molecular level. Manipulation of TLEC is encouraging for therapy of lymphatic metastasis.