Sonoda Kenzo, Miyamoto Shingo, Yamazaki Ayano, Kobayashi Hiroaki, Nakashima Manabu, Mekada Eisuke, Wake Norio
Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Cancer. 2007 Nov 1;110(9):1979-90. doi: 10.1002/cncr.23015.
The expression of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is related significantly to the overall survival of patients with various cancers. RCAS1 reportedly induces apoptotic cell death in peripheral lymphocytes, which may contribute to the escape of tumor cells from immune surveillance. RCAS1 expression also has been related to tumor invasiveness and size in uterine cervical cancer. To clarify whether RCAS1 exacerbates tumor progression, the authors investigated the association between RCAS1 expression and tumor growth potential.
The authors constructed small interfering ribonucleic acid (RNA) (siRNA) to target RCAS1. After transfection of siRNA and the RCAS1-encoding gene, growth of tumor cells was assessed in vitro and in vivo. The correlation between RCAS1 expression and angiogenesis was investigated in the transfected cells and in inoculated tumors from nude mice. In addition, the same association was investigated immunohistochemically with tissue samples from patients with uterine cervical cancer.
Knockdown of RCAS1 expression by siRNA significantly suppressed the in vivo growth of SiSo and HOUA tumor cells (P < .005); however, in vitro cell growth was not affected significantly. Enhanced RCAS1 expression significantly promoted in vivo growth, but not in vitro growth, of tumors derived from COS-7 cells (P = .0039). Introduction of the RCAS1-encoding gene increased expression of vascular endothelial growth factor (VEGF). In uterine cervical cancer, RCAS1 expression was associated significantly with VEGF expression (P = .0407) and with microvessel density (P = .0108).
RCAS1 may be a pivotal regulator of tumor growth through angiogenesis. Continued exploration of the biologic function of RCAS1 may allow the development of novel therapeutic strategies for uterine cancer.
SiSo细胞上表达的受体结合癌抗原（RCAS1）的表达与多种癌症患者的总生存期显著相关。据报道，RCAS1可诱导外周淋巴细胞凋亡，这可能有助于肿瘤细胞逃避免疫监视。RCAS1的表达也与子宫颈癌的肿瘤侵袭性和大小有关。为了阐明RCAS1是否会加剧肿瘤进展，作者研究了RCAS1表达与肿瘤生长潜能之间的关联。
作者构建了靶向RCAS1的小干扰核糖核酸（siRNA）。转染siRNA和编码RCAS1的基因后，在体外和体内评估肿瘤细胞的生长情况。研究转染细胞和裸鼠接种肿瘤中RCAS1表达与血管生成之间的相关性。此外，采用免疫组织化学方法研究子宫颈癌患者组织样本中相同的关联。
siRNA敲低RCAS1表达可显著抑制SiSo和HOUA肿瘤细胞的体内生长（P <.005）；然而，体外细胞生长未受到显著影响。增强RCAS1表达可显著促进COS-7细胞来源肿瘤的体内生长，但对体外生长无影响（P =.0039）。导入编码RCAS1的基因可增加血管内皮生长因子（VEGF）的表达。在子宫颈癌中，RCAS1表达与VEGF表达（P =.0407）和微血管密度（P =.0108）显著相关。
RCAS1可能是通过血管生成调节肿瘤生长的关键因子。持续探索RCAS1的生物学功能可能会为子宫癌开发新的治疗策略。
