Endometrial cancer invasion depends on cancer-derived tumor necrosis factor-α and stromal derived hepatocyte growth factor
Dong Soon Choi
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Deparment of Molecular Science and Technology, Ajou University, Suwon, South Korea
Search for more papers by this authorHyun-Jin Kim
Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon, South Korea
Search for more papers by this authorJong-Hyuck Yoon
Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon, South Korea
Search for more papers by this authorSeung-Chul Yoo
Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon, South Korea
Search for more papers by this authorHantae Jo
Deparment of Molecular Science and Technology, Ajou University, Suwon, South Korea
Search for more papers by this authorSo Yeon Lee
Department of Biological Sciences, Ajou University, Suwon, South Korea
Search for more papers by this authorChurl K. Min
Department of Biological Sciences, Ajou University, Suwon, South Korea
Search for more papers by this authorCorresponding Author
Hee-Sug Ryu
Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon, South Korea
Fax: +82-31-219-5245.
Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon 442-721, South KoreaSearch for more papers by this authorDong Soon Choi
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Deparment of Molecular Science and Technology, Ajou University, Suwon, South Korea
Search for more papers by this authorHyun-Jin Kim
Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon, South Korea
Search for more papers by this authorJong-Hyuck Yoon
Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon, South Korea
Search for more papers by this authorSeung-Chul Yoo
Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon, South Korea
Search for more papers by this authorHantae Jo
Deparment of Molecular Science and Technology, Ajou University, Suwon, South Korea
Search for more papers by this authorSo Yeon Lee
Department of Biological Sciences, Ajou University, Suwon, South Korea
Search for more papers by this authorChurl K. Min
Department of Biological Sciences, Ajou University, Suwon, South Korea
Search for more papers by this authorCorresponding Author
Hee-Sug Ryu
Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon, South Korea
Fax: +82-31-219-5245.
Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon 442-721, South KoreaSearch for more papers by this authorAbstract
Cancer invasion is an outcome of interactions of the cancer and the host cell. It is now becoming increasingly clear that ovarian hormones have a huge influence on such intercommunications in various types of cancers. Estrogen is known to aggravate the aggressiveness of the endometrial cancer whereas progesterone seems to act as a negative factor. Insight into the mode of ovarian hormonal actions could come from the studies of its regulation of the paracrine interactions between the endometrial cancer and the normal stromal cells during the cancer invasion. In this context, we report here that estrogen promotes the endometrial cancer invasion by inducing humoral interactions between the cancer and the stromal cells, i.e., estrogen stimulates tumor necrosis factor-α expression from the endometrial cancer cells, which, in turn, induces the stromal expression of hepatocyte growth factor (HGF), conferring the enhanced NK4 (HGF-antagonist/angiogenesis inhibitor)-sensitive invasion characteristic of the endometrial cancer cells. Additionally, we demonstrate a close correlation of the invasion of endometrial cancer cells with the expression and dimerization of integrin αvβ5 as well as the activation of focal adhesion kinase as the consequences of paracrine interactions. Thus, understanding of paracrine interactions of cancer cells with host stromal cells can yield new insight into the architecture and function of cancer invasion and metastasis, leading to a development of a new cancer therapeutic intervention. © 2008 Wiley-Liss, Inc.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
| Filename | Description |
|---|---|
| IJC_24238_sm_suppfig1.tif56.7 KB | Supporting Figure 1. HGF-mediated invasion of HEC-1A cells |
| IJC_24238_sm_suppfig2.tif215.1 KB | Supporting Figure 2. mRNA expression profiles of TNF-/a, bFGF, IL-6, and TGF-/a. HEC-1A cells or KLE cells were co-cultured with the stromal cells for 3 to 9 hr under different ovarian hormonal conditions. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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