Sun Xiaomeng, Hu Xiaojuan
Queen Mary School, Jiangxi Medical College, Nanchang University, Xuefu Avenue, Honggutan District, Nanchang 330031, China.
School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Xuefu Avenue, Honggutan District, Nanchang 330031, China.
Int J Mol Sci. 2025 Mar 27;26(7):3083. doi: 10.3390/ijms26073083.
The biomechanical properties of the extracellular matrix (ECM) including its stiffness, viscoelasticity, collagen architecture, and temperature constitute critical biomechanical cues governing breast cancer progression. Matrix metalloproteinase 13 (MMP13) is an important marker of breast cancer and plays important roles in matrix remodelling and cell metastasis. Emerging evidence highlights MMP13 as a dynamic modulator of the ECM's physical characteristics through dual mechanoregulatory mechanisms. While MMP13-mediated collagen degradation facilitates microenvironmental softening, thus promoting tumour cell invasion, paradoxically, its crosstalk with cancer-associated fibroblasts (CAFs) and tumour-associated macrophages (TAMs) drives pathological stromal stiffening via aberrant matrix deposition and crosslinking. This biomechanical duality is amplified through feedforward loops with an epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) populations, mediated by signalling axes such as TGF-β/Runx2. Intriguingly, MMP13 exhibits context-dependent mechanomodulatory effects, demonstrating anti-fibrotic activity and inhibiting the metastasis of breast cancer. At the same time, angiogenesis and increased metabolism are important mechanisms through which MMP13 promotes a temperature increase in breast cancer. Targeting the spatiotemporal regulation of MMP13's mechanobiological functions may offer novel therapeutic strategies for disrupting the tumour-stroma vicious cycle.
细胞外基质（ECM）的生物力学特性，包括其硬度、粘弹性、胶原蛋白结构和温度，构成了控制乳腺癌进展的关键生物力学信号。基质金属蛋白酶13（MMP13）是乳腺癌的一个重要标志物，在基质重塑和细胞转移中起重要作用。新出现的证据表明，MMP13通过双重机械调节机制，是ECM物理特性的动态调节因子。虽然MMP13介导的胶原蛋白降解促进了微环境的软化，从而促进肿瘤细胞的侵袭，但矛盾的是，它与癌症相关成纤维细胞（CAF）和肿瘤相关巨噬细胞（TAM）的相互作用，通过异常的基质沉积和交联驱动病理性基质硬化。这种生物力学的二元性通过由TGF-β/Runx2等信号轴介导的、与上皮-间质转化（EMT）和癌症干细胞（CSC）群体的前馈环得到放大。有趣的是，MMP13表现出依赖于环境的机械调节作用，具有抗纤维化活性并抑制乳腺癌转移。同时，血管生成和代谢增加是MMP13促进乳腺癌温度升高的重要机制。针对MMP13机械生物学功能的时空调节可能为破坏肿瘤-基质恶性循环提供新的治疗策略。
