Hara Toshiro, Murakami Yoshinori, Seiki Motoharu, Sakamoto Takeharu
Division of Cancer Cell Research, Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, 108-8639 Tokyo, Japan.
Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, 108-8639 Tokyo, Japan.
Biochem Biophys Res Commun. 2017 Aug 26;490(3):688-692. doi: 10.1016/j.bbrc.2017.06.102. Epub 2017 Jun 19.
Breast cancer is one of the most common cancers in women in the world. Although breast cancer is well treatable at the early stage, patients with distant metastases show a poor prognosis. Data from recent studies using transplantation models indicate that Mint3/APBA3 might promote breast cancer malignancy. However, whether Mint3 indeed contributes to tumor development, progression, or metastasis in vivo remains unclear. To address this, here we examined whether Mint3 depletion affects tumor malignancy in MMTV-PyMT breast cancer model mice. In MMTV-PyMT mice, Mint3 depletion did not affect tumor onset and tumor growth, but attenuated lung metastases. Experimental lung metastasis of breast cancer Met-1 cells derived from MMTV-PyMT mice also decreased in Mint3-depleted mice, indicating that host Mint3 expression affected lung metastasis of MMTV-PyMT-derived breast cancer cells. Further bone marrow transplant experiments revealed that Mint3 in bone marrow-derived cells promoted lung metastasis in MMTV-PyMT mice. Thus, targeting Mint3 in bone marrow-derived cells might be a good strategy for preventing metastasis and improving the prognosis of breast cancer patients.
乳腺癌是全球女性中最常见的癌症之一。尽管乳腺癌在早期阶段易于治疗，但发生远处转移的患者预后较差。近期使用移植模型的研究数据表明，Mint3/APBA3可能会促进乳腺癌的恶性发展。然而，Mint3在体内是否确实对肿瘤的发生、发展或转移有影响仍不清楚。为了解决这个问题，我们在此研究了Mint3缺失是否会影响MMTV-PyMT乳腺癌模型小鼠的肿瘤恶性程度。在MMTV-PyMT小鼠中，Mint3缺失不影响肿瘤的发生和生长，但会减弱肺转移。源自MMTV-PyMT小鼠的乳腺癌Met-1细胞的实验性肺转移在Mint3缺失的小鼠中也有所减少，这表明宿主Mint3的表达会影响MMTV-PyMT来源的乳腺癌细胞的肺转移。进一步的骨髓移植实验表明，骨髓来源细胞中的Mint3会促进MMTV-PyMT小鼠的肺转移。因此，针对骨髓来源细胞中的Mint3可能是预防转移和改善乳腺癌患者预后的一个良好策略。
