Abstract 2426: Differential effects of liver metastatic and brain metastatic subset of murine breast carcinoma cells

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Carcinomas are formed by heterogeneous group of cells which differ in their aggressiveness as well as metastatic potential. Understanding the characteristics of cells that form distant metastasis is crucial to design effective treatments. We previously isolated liver metastatic cells (4TLM) formed by 4THMpc murine breast carcinoma using an orthotopic model. Here we observed that 4THMpc cells also generated macroscopic brain metastasis. Cells from brain metastasis were cultured in-vitro and named as 4THM-BM in order to determine differential characteristics of brain metastatic cells from liver metastatic cells. Specifically following features were compared: 1. Metastatic characteristics after mammary pad (MP) injection; 2. The effects of conditioned medium (CM) prepared from ex-plants of primary tumors as well as cancer-associated fibroblasts (CAF) on tumor cell growth. 3. MIP-2 levels found in CM of ex-plants of primary tumors and associated fibroblasts. Methods: 4TLM and 4THM-BM cells (100000 cells /mouse) were inoculated into the right upper MP of 8-10 weeks old female Balb-c mice. Necropsies were performed 25-27 days after injection. CM of ex-plants from primary tumors and surrounding fibroblasts were prepared. Results: Cells that were previously metastasized to liver (4TLM) produced significantly more macroscopic (52.2± 8.5 vs. 16.3 ±2.84 as mean number of nodules per animal) as well as microscopic lung metastasis (12.75 ±4.26 vs. 3.17±1,1 as mean % area involved with metastatic cells per animal) compared to brain metastatic cells (4THM-BM). Similarly number of macroscopic liver metastases was significantly higher (3.4± 0,6 vs. 7,3 ±1,23 as mean number of nodules per animal) in 4TLM injected animals. CM from ex-plants of 4TLM and 4THM-BM primary tumors as well as from corresponding CAF significantly enhanced growth of 4TLM cells but not 4THM-BM cells. MIP-2 levels in CM from ex-plants of CAF were higher from CM of 4TLM and 4THM-BM primary tumors. These results not only demonstrate the heterogeneous nature of the carcinomas but also suggest that cells that metastasize to liver are more aggressive in nature and produce more visceral metastasis. MIP-2, murine equivalent to human IL-8, is involved in angiogenesis as well as inflammation and reported to be highly expressed in metastatic cells. Here we found that both primary tumors formed by metastatic cell lines and associated fibroblasts produce MIP-2 which may contribute to the metastatic behavior. Study was supported by The Scientific and Technological Research Council of Turkey (TUBITAK Grant no:109S449). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2426. doi:10.1158/1538-7445.AM2011-2426