Abstract 4965: Hypoxia has different effects on proliferation, migration and metastasis of various types of tumor cells

Abstract

Abstract Hypoxia promotes angiogenesis and assigns radio- and chemotherapy resistance and aggressive phenotype to tumor cells. HIF-1 alpha, the main regulator of hypoxia induced processes, is activated in areas of low oxygen supply. Rho GTPases such as Rac1, cdc42 and RhoA play an important role in actin polimerization, depolimerization and stress fiber formation during tumor morphogenesis, cell adhesion, and cell migration. In the present study cell lines of melanoma (HT168-M1), fibrosarcoma (HT1080), colon cancer (HT25, HT29), lung cancer (H1975) and a head-neck cancer (PECA-PJ15) were cultured under normoxic and hypoxic conditions containing 1% and 5% O2. Proliferation tests with sulforhodamine B, migration assays with modified Boyden chamber and time-lapse videomicroscopy were performed with all cell lines. Furthermore, investigation of the expression and localization of HIF-1alpha, Rac1, cdc42 and RhoA mRNA by quantitative RT-PCR and immunfluorescence and the activation of small GTPases were performed. In addition, we examined the role of the hypoxic condition (CoCl2 administration) and HIF blockade (chetomin administration) on the metastatic potential of tumor cells using orthotopic xenograft models. The various tumor cell lines displayed different behaviour in vitro and in vivo. In the case of the most motile cell line (HT-168-M1), proliferation and migration capacity, moreover the gene expression patterns of small GTPases and HIF-1alpha were significantly higher under hypoxic conditions compared to normoxic cells. Migration capacity of the PECA-PJ15 cell line was higher when cultured under higher oxygen concentration. The hypoxic condition was less tolerated by both human colon carcinoma cell lines. In HT29 cells RhoA translocated into the nucleus under the hypoxic condition. The in vivo experiments demonstrated that primary tumor size and the number of metastasis were the largest in the CoCl2-treated group, and the smallest in the chetomin-treated group. In conclusion, our findings support that different phenotypes of the cancer cells form under hypoxia presumably via different pathways. This work is supported by OTKA K84173. Citation Format: Enikő Tátrai, Alexandra Bartal, Zsuzsanna Fehér, Ákos Farkas, Sándor Paku, István Kenessey, József Tóvári. Hypoxia has different effects on proliferation, migration and metastasis of various types of tumor cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4965. doi:10.1158/1538-7445.AM2014-4965