Normalization of the tumor microenvironment: evidence for tissue inhibitor of metalloproteinase-2 as a cancer therapeutic.

Abstract:

:Matrix metalloproteinases (MMPs) are members of the Metzincin family of proteases responsible for degrading the extracellular matrix (ECM). In early studies, MMP degradation of the sub-epithelial basement membrane was thought to be tumor cell autonomous and contribute to the invasive behavior of malignant cells. It is now recognized that MMPs have multiple roles that can either promote or inhibit tumor progression and metastasis. The endogenous inhibitors of the MMPs are the tissue inhibitors of metalloproteinases (TIMPs). Early studies on the tumor microenvironment revealed TIMP function to be principally through the inhibition of MMPs, thereby blocking tumor cell migration and invasion. However, data from a number of laboratories are now reporting that TIMPs have direct cellular functions, independent of their MMP inhibitory activity. The TIMPs can modulate normal tissue physiology and development, as well as pathology and progression in a variety of acute and chronic disease states. In this review, we briefly describe the role of MMPs and TIMPs in ECM turnover and formation of the tumor microenvironment. Based on the evidence presented, we postulate that TIMP-2 and other soluble components of the normal ECM may provide a novel therapeutic approach to cancer treatment through "normalization" of the tumor microenvironment.

journal_name

Connect Tissue Res

authors

Stetler-Stevenson WG,Gavil NV

doi

10.3109/03008207.2013.867339

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

13-9

issue

1

eissn

0300-8207

issn

1607-8438

journal_volume

55

pub_type

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