Targeting early lesion in breast cancer is more therapeutically effective. We have previously identified an oncoprotein GT198 (PSMC3IP) in human breast cancer. Here we investigated GT198 in MMTV-PyMT mouse mammary gland tumors and found that GT198 is a shared early lesion in both species. Similar to human breast cancer even before a tumor appears, cytoplasmic GT198 is overexpressed in mouse tumor stroma including pericyte stem cells, descendent adipocytes, fibroblasts, and myoepithelial cells. Using recombinant GT198 protein as an antigen, we vaccinated MMTV-PyMT mice and found that the GT198 vaccine delayed mouse tumor growth and reduced lung metastasis. The antitumor effects were linearly correlated with vaccinated mouse serum titers of GT198 antibody, which recognized cell surface GT198 protein on viable tumor cells confirmed by FACS. Furthermore, GT198+ tumor cells isolated from MMTV-PyMT tumor induced faster tumor growths than GT198- cells when re-implanted into normal FVB/N mice. Together, this first study of GT198 vaccine in mouse showed its effectiveness in antitumor and anti-metastasis. The finding supports GT198 as a potential target in human immunotherapy since GT198 defect is shared in both human and mouse.

中文翻译：

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癌蛋白GT198疫苗接种可延迟MMTV-PyMT小鼠的肿瘤生长。

靶向乳腺癌的早期病变在治疗上更有效。我们先前已经确定了人类乳腺癌中的癌蛋白GT198（PSMC3IP）。在这里，我们调查了MMTV-PyMT小鼠乳腺肿瘤中的GT198，发现GT198是这两个物种中共有的早期病变。与人类乳腺癌相似，甚至在肿瘤出现之前，胞浆GT198在小鼠肿瘤基质中就过表达，其中包括周细胞干细胞，后代脂肪细胞，成纤维细胞和肌上皮细胞。使用重组GT198蛋白作为抗原，我们给MMTV-PyMT小鼠接种了疫苗，发现GT198疫苗延迟了小鼠肿瘤的生长并减少了肺转移。抗肿瘤作用与疫苗接种的小鼠血清GT198抗体滴度呈线性相关，该抗体可通过FACS确认可存活肿瘤细胞上的细胞表面GT198蛋白。此外，当重新植入正常FVB / N小鼠中时，从MMTV-PyMT肿瘤中分离出的GT198 +肿瘤细胞比GT198-细胞诱导出更快的肿瘤生长。总之，这项对小鼠GT198疫苗的首次研究显示了它在抗肿瘤和抗转移方面的有效性。该发现支持GT198作为人类免疫治疗的潜在靶标，因为GT198缺陷在人类和小鼠中均存在。