Precision Medicine Branch, Research Institute, National Cancer Center, 323 Ilsanro, Goyang, Gyeonggi-do, 10408, Republic of Korea.
Department of Environmental Medical Biology, Institute of Tropical Medicine, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
Sci Rep. 2017 Jul 10;7(1):4930. doi: 10.1038/s41598-017-05247-7.
Gastric cancer is the third most common cause of cancer mortality, and the survival rate of stage IV advanced gastric cancer (AGC) patients with distant metastasis is very low. Thus, the detection and eradication of disseminated cancer cells by targeting cell surface molecules in AGC would improve patient survival. The hyaluronic acid receptor, CD44, has various isoforms generated by alternative splicing, and some isoforms are known to be correlated to gastric cancer. In this study, to find out the most appropriate CD44v for targeting AGC, we analysed the expression differences of CD44 isoforms at the mRNA level in stomach cancer cell lines as well as in 74 patients with AGC by using exon-specific qRT-PCR. Among the CD44v isoforms, CD44v8-10 was determined as the most promising biomarker for the development of theranostic agents of gastric cancer. Next, we synthesised the conjugate of anti-CD44v9 antibody with near-infrared fluorophore or photosensitiser, and then demonstrated its feasibility for target cell-specific imaging and photoimmunotherapy in gastric cancer. As a result, these conjugates have clearly demarcated the surface of CD44v8-10 expressing cancer cells and showed efficient phototoxic effects. Therefore, this study revealed that CD44v8-10 is the efficient theranostic biomarker to target disseminated cancer cells in AGC.
胃癌是癌症死亡的第三大常见原因，而伴有远处转移的 IV 期晚期胃癌（AGC）患者的生存率非常低。因此，通过针对 AGC 细胞表面分子检测和消除播散的癌细胞，将提高患者的生存率。透明质酸受体 CD44 具有通过选择性剪接产生的各种异构体，其中一些异构体与胃癌相关。在这项研究中，为了找到最适合靶向 AGC 的 CD44v，我们通过外显子特异性 qRT-PCR 分析了胃癌细胞系和 74 例 AGC 患者中 CD44 异构体在 mRNA 水平上的表达差异。在 CD44v 异构体中，CD44v8-10 被确定为胃癌治疗药物开发最有前途的生物标志物。接下来，我们合成了抗 CD44v9 抗体与近红外荧光团或光敏剂的缀合物，然后证明了其在胃癌中用于靶细胞特异性成像和光免疫治疗的可行性。结果表明，这些缀合物清晰地标定了表达 CD44v8-10 的癌细胞表面，并表现出有效的光毒性作用。因此，这项研究表明 CD44v8-10 是靶向 AGC 中播散癌细胞的有效治疗生物标志物。
