Mima Kosuke, Okabe Hirohisa, Ishimoto Takatsugu, Hayashi Hiromitsu, Nakagawa Shigeki, Kuroki Hideyuki, Miyake Keisuke, Takamori Hiroshi, Beppu Toru, Baba Hideo
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
Oncol Lett. 2012 May;3(5):1047-1051. doi: 10.3892/ol.2012.611. Epub 2012 Feb 17.
The finding that the expression of a variant isoform of CD44 induced a metastatic phenotype in locally growing tumor cells has attracted considerable attention. A number of studies have analyzed the expression of CD44v6 in human tumors of different origins. However, the findings of these studies have been controversial. Therefore, in the present study, we assessed the association between CD44v6 expression and the invasive capacity of hepatocellular carcinoma (HCC) cell lines and also investigated the clinical significance of CD44v6 in 150 HCC patients by immunohistochemical analysis. The HCC cell lines with a high CD44v6 expression, including HLF, HLE and SK HEP-1, showed high invasive potential, whereas those with a low CD44v6 expression, including PLC/PRF/5 and HuH1, showed low invasiveness. Despite these observations, we did not find any significant correlation between CD44v6 expression and clinicopathological factors in patients. By contrast, there was a weak correlation between a low CD44v6 expression and vascular invasion in HCC patients (P=0.080). Kaplan-Meier curves revealed that a high CD44v6 expression was not significantly associated with disease-free survival (P=0.736) or overall survival (P=0.736). Our study suggests that the expression levels of CD44v6 are correlated with the invasiveness of HCC in vitro, but do not appear to be clinically significant. Future experiments should investigate the role of the various CD44 isoforms, including the CD44 standard isoform, in HCC cell lines and in patients with HCC.
CD44变异体同工型的表达在局部生长的肿瘤细胞中诱导转移表型这一发现引起了广泛关注。许多研究分析了CD44v6在不同起源的人类肿瘤中的表达。然而,这些研究的结果存在争议。因此,在本研究中,我们评估了CD44v6表达与肝癌(HCC)细胞系侵袭能力之间的关联,并通过免疫组织化学分析研究了150例HCC患者中CD44v6的临床意义。CD44v6高表达的HCC细胞系,包括HLF、HLE和SK HEP-1,显示出高侵袭潜能,而CD44v6低表达的细胞系,包括PLC/PRF/5和HuH1,则显示出低侵袭性。尽管有这些观察结果,但我们未发现患者中CD44v6表达与临床病理因素之间存在任何显著相关性。相比之下,HCC患者中CD44v6低表达与血管侵犯之间存在弱相关性(P=0.080)。Kaplan-Meier曲线显示,CD44v6高表达与无病生存期(P=0.736)或总生存期(P=0.736)均无显著相关性。我们的研究表明,CD44v6的表达水平与体外HCC的侵袭性相关,但似乎不具有临床意义。未来的实验应研究包括CD44标准同工型在内的各种CD44同工型在HCC细胞系和HCC患者中的作用。