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J Oral Pathol Med (2010) 39 168–175 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. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate invasion- and metastasis-related genes in gastric cancer. To this end, we used the transwell system to select a highly invasive subcell line from minimally invasive parent cells and compared gene expression in paired cell lines with high- and low-invasive potentials. Lysyl oxidase-like 2 (LOXL2) was overexpressed in the highly invasive subcell line. Immunohistochemical analysis revealed that LOXL2 expression was markedly increased in carcinoma relative to normal epithelia, and this overexpression in primary tumor was significantly associated with depth of tumor invasion, lymph node metastasis and poorer overall survival. Moreover, LOXL2 expression was further increased in lymph node metastases compared with primary cancer tissues. RNA interference-mediated knockdown and ectopic expression of LOXL2 showed that LOXL2 promoted tumor cell invasion in vitro and increased gastric carcinoma metastasis in vivo. Subsequent mechanistic studies showed that LOXL2 could activate both the Snail/E-cadherin and Src kinase/Focal adhesion kinase (Src/FAK) pathways. However, secreted LOXL2 induced gastric tumor cell invasion and metastasis exclusively via the Src/FAK pathway. Expression correlation analysis in gastric carcinoma tissues also revealed that LOXL2 promoted invasion via the Src/FAK pathway but not the Snail/E-cadherin pathway. We then evaluated secreted LOXL2 as a target for gastric carcinoma treatment and found that an antibody against LOXL2 significantly inhibited tumor growth and metastasis. Overall, our data revealed that LOXL2 overexpression, a frequent event in gastric carcinoma progression, contributes to tumor cell invasion and metastasis, and LOXL2 may be a therapeutic target for preventing and treating metastases. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]