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Stromal metalloproteinases: Crucial contributors to the tumor microenvironment
Author(s) -
Shimoda Masayuki,
Ohtsuka Takashi,
Okada Yasunori,
Kanai Yae
Publication year - 2021
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1111/pin.13033
Subject(s) - stromal cell , matrix metalloproteinase , extracellular matrix , tumor microenvironment , metastasis , cancer research , microbiology and biotechnology , tumor progression , biology , inflammation , crosstalk , proteolytic enzymes , tissue remodeling , immune system , cancer , immunology , enzyme , biochemistry , genetics , physics , optics
Proteolytic balance is crucial for the maintenance of tissue homeostasis. In cancer, dysregulated proteolysis is involved in unregulated tissue remodeling and inflammation, leading to the promotion of tumor growth, local invasion, and metastasis. Metalloproteinases, which were first identified as collagen cleaving enzymes, have been shown to extensively degrade extracellular matrix proteins or selectively release cell surface‐bound cytokines, growth factors, or their receptors, thereby impacting extracellular matrix integrity, immune cell recruitment and tissue turnover. Although tumor cells produce various metalloproteinases, the major source is thought to be stromal cells infiltrating the tumor. Different types of stromal cells express specific sets of metalloproteinases and their inhibitors, which specifically alter the milieu within the tumor. In this review, recent findings and knowledge regarding metalloproteinases derived from stromal cells during the creation of the tumor microenvironment are described and their contribution to the tumor progression and metastasis discussed.