Carbonic anhydrase-related protein VIII increases invasiveness of non-small cell lung adenocarcinoma
Carbonic anhydrase-related protein VIII increases invasiveness of non-small cell lung adenocarcinoma
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DOI：
10.1007/s00428-006-0199-0
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发表时间：
2006-06-01
期刊：
影响因子：
3.5
通讯作者：
Onishi, Saburo
中科院分区：
文献类型：
--
作者：
Ishihara, Tsuyoshi;Takeuchi, Tamotsu;Onishi, Saburo
碳酸酐酶相关蛋白VIII(Carp VIII)被认为是一种癌胎儿抗原，在结直肠癌和非小细胞肺癌中过表达。然而，CA-RP VIII在肺癌中的病理生物学特性仍不清楚。在本研究中，我们检测了外源性CA-RP表达对高分化肺腺癌细胞系PC-9的超微结构的影响。表达CA-RP VIII的PC-9细胞胞浆内可见大量纤毛排列的空泡，有时大空泡将胞核推向一侧，而对照PC-9细胞则未见。此外，在表达CA-RP VIII的PC-9细胞中，可见含有丰富胞浆粘蛋白的印戒细胞，而在对照PC-9细胞中则很少。我们随后检测了CA-RP VIII在非典型腺瘤性增生和早期肺腺癌(Ia期)中的表达。Carp VIII在浸润性肺腺癌中有显著表达，而在非侵袭性腺癌中无明显表达。有趣的是，CA-RP VIII在印戒细胞癌和浸润性粘液腺癌成分中强烈表达。在Matrigel侵袭实验中，CA-RP也能增强PC-9细胞的侵袭力。提示CA-RP VIII在肺腺癌中的表达与癌细胞侵袭有关。
Carbonic anhydrase-related protein VIII (CARP VIII) is believed to be an oncofetal antigen and is overexpressed in colorectal and non-small cell lung cancer. However, the pathobiological properties of CA-RP VIII in lung cancer remain unclear. In the present study, we examined ultrastructural changes caused by exogenous CA-RP VIII expression in a well-differentiated lung adenocarcinoma cell line, PC-9. Many vacuoles lined by cilia, sometimes large vacuoles pushing the nuclei to one side, were found in the cytoplasm of CA-RP VIII-expressing PC-9 cells, but not in control PC-9 cells. Moreover, signet-ring cells containing abundant intracytoplasmic mucin were often found among CA-RP VIII-expressing PC-9 cells, but rarely among control PC-9 cells. We subsequently examined CA-RP VIII expression in atypical adenomatous hyperplasia and early-stage lung adenocarcinoma (Stage Ia). Significant expression of CARP VIII was observed in invasive lung adenocarcinoma but not in noninvasive adenocarcinoma. Interestingly, CA-RP VIII was strongly expressed in signet-ring cell cancer and invasive mucinous adenocarcinoma components. CA-RP VIII also appeared to enhance the invasiveness of PC-9 cells in Matrigel invasion assay. The present findings suggest that CA-RP VIII expression in lung adenocarcinoma is related to cancer cell invasion.