Matricellular proteins: from homeostasis to inflammation, cancer, and metastasis

Abstract

The family of matricellular proteins comprises molecules with disparate biology. The main characteristic of matricellular proteins is to be expressed during tissue renewal and repair in order to "normalize" the tissue. Tumors are wound that do not heal, and tumor growth and metastasis can be viewed as a consequence of aberrant homeostasis, during which matricellular proteins are often upregulated. In the tumor microenvironment, they can be produced by both tumor cells and surrounding stromal cells, such as fibroblasts and macrophages. In this context, matricellular proteins can exert several functions that actively contribute to tumor progression. They may (a) regulate cellular adhesion and migration and extracellular matrix deposition, (b) control tumor infiltration by macrophages or other leukocytes, (c) affect tumor angiogenesis, (d) regulate TGFbeta and other growth factor receptor signals, (e) directly stimulate integrin receptors to transduce pro-survival or pro-migratory signals, and (f) regulate the wnt/beta-catenin pathways. Most of these functions contribute to settle a chronic low inflammatory state, whose involvement in tissue transformation and tumor progression is now established.

SPARC Oppositely Regulates Inflammation and Fibrosis in Bleomycin-Induced Lung Damage

“…35,36 An impaired ECM deposition or the absence of SPARC is associated with increased inflammatory infiltration and immune cell migration. 10,37,38 This finding has prompted the idea that SPARC might be involved in the regulation of inflammatory response as partially demonstrated in ovarian cancer, where SPARC normalizes the tumor microenvironment by regulating cytokine production. 12 In Sparc Ϫ/Ϫ mice inflammation is greater than in their WT counterparts.…”

Emerging Roles of Angiopoietin-like 4 in Human Cancer

“…Ongoing cancer research focusing on understanding the interaction of cancer cells with their microenvironment has intensified over recent years, and a new class of proteins known as matricellular proteins have since been implicated (4)(5)(6). Matricellular proteins are a group of nonstructural, extracellular matrix (ECM)-associated glycoproteins secreted by cancer cells and neighboring stromal cells into the extracellular environment (4,5).…”

“…Matricellular proteins are a group of nonstructural, extracellular matrix (ECM)-associated glycoproteins secreted by cancer cells and neighboring stromal cells into the extracellular environment (4,5). This large group of structurally and functionally diverse proteins modulates cellmatrix interactions and cell functions by interacting with membrane receptors, proteases, hormones, and other bioeffector molecules, as well as with structural matrix proteins such as collagen and vitronectin (7,8).…”

“…This large group of structurally and functionally diverse proteins modulates cellmatrix interactions and cell functions by interacting with membrane receptors, proteases, hormones, and other bioeffector molecules, as well as with structural matrix proteins such as collagen and vitronectin (7,8). Recent studies have implicated several members of matricellular proteins, such as osteopontin, secreted protein acidic and rich in cysteine, and angiopoietin-like 4 (ANGPTL4) as important factors in tumor progression (4,(9)(10)(11). Of particular interest, ANGPTL4 is a novel matricellular protein that was reported to interact with specific ECM proteins and integrins to facilitate cell migration during wound healing (7,8).…”

Nuclear co-localization and functional interaction of COX-2 and HIF-1α characterize bone metastasis of human breast carcinoma

“…The current most recognized theory for metastasis engraftment is the metastatic niche model, presuming that the tumor cell does not solely dictate its own fate but that the formation of a hospitable microenvironment is essential-not just permissive-to enable a disseminating tumor cell to spawn a secondary tumor growth [4]. These niches form as a result of factors secreted by tumor and stroma cells, and can either be newly induced or be adaptations of pre-existing physiological niches, such as stem cell niches of hematopoietic organs [1,5].…”