Abstract 2276: Oncostatin M promotes breast cancer metastasis to lung by affecting initial stages of metastasis
| Autor: | Cheryl L. Jorcyk, Jordan Koncinsky, Celeste Bolin, Ken Tawara |
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| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | Cancer Research. 75:2276-2276 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2015-2276 |
| Popis: | Recent studies suggest that cancer cells destined to establish metastatic lesions may shed early during tumor development, potentially even from carcinoma in situ. Furthermore, these cells may disseminate and lay dormant in a metastatic microenvironment (MME) for years before macrometastases are detectable. While inflammatory cytokines are known to be important in promoting breast cancer metastasis, their effect on tumor cell dissemination needs to be clarified. In this study, we investigate the effect of the interleukin-6-related, inflammatory cytokine oncostatin M (OSM) on early stages of breast cancer metastasis. First, we establish the expression pattern of OSM in human breast tissue using tissue microarrays. OSM is expressed in epithelial cells at higher levels in invasive ductal carcinoma (IDC) than in adjacent normal breast tissue, but is expressed at highest levels in ductal carcinoma in situ (DCIS). This suggests that autocrine-produced OSM may be important in breast tumor invasion and in the promotion of initial steps of metastasis. OSM increases early stage metastatic potential in vitro in aggressive 4T1.2 triple negative breast cancer cells (TNBCs) by inducing tumor cell detachment and migration. These findings are corroborated by in vivo studies using an orthotopic 4T1.2 mouse model of breast cancer. Reduced OSM expression in 4T1.2 (4T1.2-shOSM) cells is sufficient to inhibit the progression and the final number and volume of metastases in the lung, as well as circulating tumor cell (CTC) numbers in Balb/c mice. The number of CTCs is further reduced in a Balb/c OSM knockout background, demonstrating the importance of both paracrine- and autocrine-produced OSM in this process. Furthermore, orthotopic injection of 4T1.2-shOSM cells increases animal survival post-primary tumor resection, while bypassing the early stages of metastasis by injecting cells directly into the systemic circulation does not. As expected, in an orthotopic xenograft MDA-MB-231 human breast cancer mouse model, peri-tumoral injection of recombinant OSM increases the number of CTCs as well as spontaneous metastasis to lung. Taken together, these results suggest that suppression of OSM levels in the tumor microenvironment could be a highly effective therapeutic strategy for halting breast cancer metastasis to lung. Citation Format: Ken Tawara, Celeste Bolin, Jordan Koncinsky, Cheryl L. Jorcyk. Oncostatin M promotes breast cancer metastasis to lung by affecting initial stages of metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2276. doi:10.1158/1538-7445.AM2015-2276 |
| Databáze: | OpenAIRE |
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