Witkiewicz Agnieszka K, Casimiro Mathew C, Dasgupta Abhijit, Mercier Isabelle, Wang Chenguang, Bonuccelli Gloria, Jasmin Jean-François, Frank Philippe G, Pestell Richard G, Kleer Celina G, Sotgia Federica, Lisanti Michael P
Stem Cell Biology and Regenerative Medicine Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Cell Cycle. 2009 Jun 1;8(11):1654-8. doi: 10.4161/cc.8.11.8544.
Here, we discuss recent evidence that an absence of stromal Cav-1 expression in human breast cancers is a powerful single independent predictor of early disease recurrence, metastasis and poor clinical outcome. These findings have now been validated in two independent patient populations. Importantly, the predictive value of stromal Cav-1 is independent of epithelial marker status, making stromal Cav-1 a new "universal" or "widely-applicable" breast cancer prognostic marker. We propose based on the expression of stromal Cav-1, that breast cancer patients could be stratified into high-risk and low-risk groups. High-risk patients showing an absence of stromal Cav-1 should be offered more aggressive therapies, such as anti-angiogenic approaches, in addition to the standard therapy regimens. Mechanistically, loss of stromal Cav-1 is a surrogate biomarker for increased cell cycle progression, growth factor secretion, "stemness", and angiogenic potential in the tumor microenvironment. Since almost all cancers develop within the context of a stromal microenvironment, this new stromal classification system may be broadly applicable to other epithelial and non-epithelial cancer subtypes, as well as "pre-malignant" lesions (carcinoma in situ).
在此，我们讨论近期的证据，即人类乳腺癌中基质Cav-1表达缺失是早期疾病复发、转移及不良临床结局的有力单一独立预测指标。这些发现现已在两个独立的患者群体中得到验证。重要的是，基质Cav-1的预测价值独立于上皮标志物状态，这使得基质Cav-1成为一种新的“通用”或“广泛适用”的乳腺癌预后标志物。基于基质Cav-1的表达，我们建议可将乳腺癌患者分为高危和低危组。基质Cav-1表达缺失的高危患者除接受标准治疗方案外，还应接受更积极的治疗，如抗血管生成疗法。从机制上讲，基质Cav-1缺失是肿瘤微环境中细胞周期进程加快、生长因子分泌增加、“干性”及血管生成潜能增强的替代生物标志物。由于几乎所有癌症都在基质微环境中发生，这种新的基质分类系统可能广泛适用于其他上皮和非上皮癌亚型，以及“癌前”病变（原位癌）。
