期刊
INTERNATIONAL JOURNAL OF CANCER
卷 125, 期 2, 页码 257-263出版社
WILEY
DOI: 10.1002/ijc.24330
关键词
endometrial cancer; animal model; orthotopic implantation; metastasis; RUNX1
类别
资金
- Marato TV3 [050431]
- Ministerio de Educacion y Ciencia [SAF 2008-03996]
- Fondo de Investigaciones Saintarias [99/0897, 01/10076, 02/0733, 05/00240]
- Departament de Universitats
- de Recerca i de Societat de la Informacio de la Generalitat de Catalunya [2005SGR00553]
- Instituto de Salud Carlos III [RTIC RD06/0020/0058]
- Institut Catala de la Salut
Endometrial carcinoma is the most common malignancy of the female genital tract in industrialized countries. Metastasis is the major cause of endometrial cancer deaths. Therefore, there is a vital need for clinically relevant in vivo models allowing the elucidation of the molecular and cellular mechanisms underlying metastatic behavior. In this study, we describe an innovative experimental orthotopic model of human endometrial carcinoma. Implantation in the bifurcation of the uterine horns resulted in tumors integrated into the myometrial compartment, which can be used and further exploited for the study of in vivo angiogenesis, myometrial invasion, and the metastatic capacity of endometrial cancer cells. This orthotopic model also represents a suitable tool to analyze how tumorigenesis and distant metastasis of endometrial cancer might be influenced by gene alteration, by modulating its expression in the original cancer cell line. One of the candidate genes implicated in endometrial cancer is the transcription factor RUNX1. The over-expression of RUNX1 in the endometrial cancer cell line HEC1A and the transplantation of these cells to the uterus of nude mice were associated specifically with distant metastasis in the lung. RUNX1 plays a role in the establishment of metastases in endometrial cancer. Translated to the clinics, these models would be equivalent to an advanced undifferentiated carcinoma with node affectation (stage ITIC) and distant metastasis (stage IVB). These patients would be candidates for adjuvant therapy, not efficient until today, and therefore, our models are actually suitable for the design and evaluation of experimental therapies. (C) 2009 UICC
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