Tryggvason K, Höyhtyä M, Pyke C
Biocenter, University of Oulu, Finland.
Breast Cancer Res Treat. 1993;24(3):209-18. doi: 10.1007/BF01833261.
The matrix metalloproteinases appear to be elevated in tumors with metastatic potential, and may well be involved in penetration of the basement membrane and degradation of extracellular proteins including type IV collagen. An imbalance between the 72 kDa and 92 kDa type IV collagenases and the associated tissue inhibitors of these metalloproteinases (TIMPs) may therefore have a role in the invasive phenotype. Cultured tumor cells with invasive potential secrete both type IV collagenases, though in tumors there is some evidence that the 72 kDa form at least may be produced by stromal cells at the invading tumor front rather than primarily by the tumor cells themselves, while the 92 kDa form may be synthesized in macrophages near the front. These collagenases are elevated in invasive as compared with in situ tumor components, but their specific roles and prognostic significance are not yet established.
基质金属蛋白酶在具有转移潜能的肿瘤中似乎会升高,很可能参与基底膜的穿透以及包括IV型胶原在内的细胞外蛋白的降解。因此,72 kDa和92 kDa IV型胶原酶与这些金属蛋白酶的相关组织抑制剂(TIMPs)之间的失衡可能在侵袭性表型中起作用。具有侵袭潜能的培养肿瘤细胞会分泌两种IV型胶原酶,不过在肿瘤中,有一些证据表明,至少72 kDa形式可能是由侵袭性肿瘤前沿的基质细胞产生的,而不是主要由肿瘤细胞自身产生,而92 kDa形式可能是在前沿附近的巨噬细胞中合成的。与原位肿瘤成分相比,这些胶原酶在侵袭性肿瘤中升高,但其具体作用和预后意义尚未明确。