Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.
Cell Cycle. 2013 Aug 15;12(16):2684-90. doi: 10.4161/cc.25794. Epub 2013 Jul 29.
The progression from in situ to invasive breast carcinoma is still an event poorly understood. However, it has been suggested that interactions between the neoplastic cells and the tumor microenvironment may play an important role in this process. Thus, the determination of differential tumor-stromal metabolic interactions could be an important step in invasiveness. The expression of stromal Caveolin-1 (Cav-1) has already been implicated in the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). Additionally, stromal Cav-1 expression has been associated with the expression of stromal monocarboxylate transporter 4 (MCT4) in invasive breast cancer. However, the role of stromal MCT4 in invasiveness has never been explored, neither the association between Cav-1 and MCT4 in the transition from breast DCIS to IDC. Therefore, our aim was to investigate in a series of breast cancer samples including matched in situ and invasive components, if there was a relationship between stromal Cav-1 and MCT4 in the progression from in situ to invasive carcinoma. We found loss of stromal Cav-1 in the progression to IDC in 75% of the cases. In contrast, MCT4 stromal expression was acquired in 87% of the IDCs. Interestingly, a concomitant loss of Cav-1 and gain of MCT4 was observed in the stroma of 75% of the cases, when matched in situ and invasive carcinomas were compared. These results suggest that alterations in Cav-1 and MCT4 may thus mark a critical point in the progression from in situ to invasive breast cancer.
从原位癌到浸润性乳腺癌的进展仍然是一个了解甚少的事件。然而，已经有人提出，肿瘤细胞与肿瘤微环境之间的相互作用可能在这个过程中发挥重要作用。因此，确定肿瘤基质代谢的差异相互作用可能是侵袭性的重要步骤。基质 Cav-1（Cav-1）的表达已经与从导管原位癌（DCIS）到浸润性导管癌（IDC）的进展有关。此外，基质 Cav-1 的表达与浸润性乳腺癌中基质单羧酸转运蛋白 4（MCT4）的表达有关。然而，基质 MCT4 在侵袭性中的作用从未被探索过，也从未探讨过从乳腺 DCIS 到 IDC 转变过程中 Cav-1 和 MCT4 之间的关联。因此，我们的目的是在一系列包括原位和浸润性成分的乳腺癌样本中研究，如果在从原位癌到浸润性癌的进展过程中存在基质 Cav-1 和 MCT4 之间的关系。我们发现，在 75%的情况下，基质 Cav-1 在向 IDC 进展过程中丢失。相比之下，MCT4 基质表达在 87%的 IDC 中获得。有趣的是，当比较匹配的原位癌和浸润性癌时，在 75%的病例中观察到基质 Cav-1 的同时丢失和 MCT4 的获得。这些结果表明，Cav-1 和 MCT4 的改变可能标志着从原位到浸润性乳腺癌进展的一个关键转折点。
