Mmp2, a Zn2+-dependent metalloproteinase, plays a crucial role in multiple biological processes. It is involved in extracellular matrix remodeling and is associated with pathways related to cancer, angiogenesis, and immune responses in the tumor microenvironment. Genetic models, such as KO/CKO mouse models, can be valuable for studying its functions.

In melanoma tumorigenesis, Mmp2 signals proinflammatory pathways on antigen-presenting cells, requiring TLR2 and TLR4. Mmp2 overexpression in B16 cells promotes rapid tumor growth, accompanied by reduced intratumoral cytolytic cells and increased M2 macrophages, while Mmp2 knockdown slows tumor growth and enhances T-cell proliferation and NK-cell recruitment. These effects are mediated through dysfunctional DC-T cell cross-talk [1]. In breast cancer, Mmp2 overexpression is associated with an unfavorable overall survival, a higher risk of distant metastasis, and is related to higher clinical stage and histological grade [2]. In gastric cancer, MMP2-positive patients display a shorter overall survival than MMP2-negative patients, and abnormal MMP2 expression may be a strong indicator of poor prognosis [3].

In conclusion, Mmp2 is essential in extracellular matrix-related processes and significantly impacts cancer development and immune responses in the tumor microenvironment. Studies using gene-knockout or conditional-knockout mouse models have revealed its role in melanoma, breast cancer, and gastric cancer, providing valuable insights into disease mechanisms and potential therapeutic targets.

References:

1. Muniz-Bongers, Luciana R, McClain, Christopher B, Saxena, Mansi, Merad, Miriam, Bhardwaj, Nina. 2021. MMP2 and TLRs modulate immune responses in the tumor microenvironment. In JCI insight, 6, . doi:10.1172/jci.insight.144913. https://pubmed.ncbi.nlm.nih.gov/34032639/

2. Jiang, Hanfang, Li, Huiping. 2021. Prognostic values of tumoral MMP2 and MMP9 overexpression in breast cancer: a systematic review and meta-analysis. In BMC cancer, 21, 149. doi:10.1186/s12885-021-07860-2. https://pubmed.ncbi.nlm.nih.gov/33568081/

3. Wang, He-Ling, Zhou, Ping-Yi, Zhang, Yu, Liu, Peng. 2014. Relationships between abnormal MMP2 expression and prognosis in gastric cancer: a meta-analysis of cohort studies. In Cancer biotherapy & radiopharmaceuticals, 29, 166-72. doi:10.1089/cbr.2014.1608. https://pubmed.ncbi.nlm.nih.gov/24784911/