Distinct Populations of Stromal Cells Express Collagenase-3 (MMP-13) and Collagenase-1 (MMP-1) in Chronic Ulcers but Not in Normally Healing Wounds

Vaalamo, Maarit; Mattila, Laura; Johansson, Nina; Kariniemi, Arja‐Leena; Karjalainen–Lindsberg, Marja-Liisa; Kähäri, Veli‐Matti; Saarialho–Kere, Ulpu

doi:10.1111/1523-1747.ep12276722

Cited by 244 publications

(230 citation statements)

References 26 publications

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“…MMP-1 and -13 are uniquely expressed for epithelial cell regrowth (re-epithelialization) and tissue remodeling in chronic wounds, respectively. 62 Perhaps carcinoma cell growth without motility (ie, epithelial cell regrowth) is supported in part by MMP-1 but not MMP-13 expression, while tumor cell motility/invasion and mechanisms, used during chronic wound repair, require selective MMP-1 and MMP-13 activity.…”

Section: Cxcr4-mediated Pca Migration and Invasionmentioning

confidence: 99%

CXCL12–CXCR4 interactions modulate prostate cancer cell migration, metalloproteinase expression and invasion

Singh

Grizzle

et al. 2004

Laboratory Investigation

213

187

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The mechanisms responsible for prostate cancer metastasis are incompletely understood at both the cellular and molecular levels. In this regard, chemokines are a family of small, cytokine-like proteins that induce motility of neoplastic cells, leukocytes and cancer cells. The current study evaluates the molecular mechanisms of CXCL12 and CXCR4 in prostate cancer cell migration and invasion. We report that functional CXCR4 is significantly expressed by prostate cancer cell lines, LNCaP and PC3, when compared with normal prostatic epithelial cells (PrEC). As measured using motility and invasion chamber assays, prostate cancer cells migrated and invaded through extracellular matrix components in response to CXCL12, at rates that corresponded to CXCR4 expression. Anti-CXCR4 antibodies (Abs) significantly impaired the migration and invasive potential of PC3 and LNCaP cells. CXCL12 induction also enhanced collagenase-1 (metalloproteinase-1 (MMP-1)) expression by LNCaP and PC3 cells. Collagenase-3 (MMP-13) was expressed by prostate cancer cells, but it was not expressed by PrEC cells or modulated by CXCL12. CXCL12 increased MMP-2 expression by LNCaP and PC3; however, MMP-9 expression was elevated only in PC3 cells after CXCL12-CXCR4 ligation. PC3 cells also expressed high levels of stromelysin-1 (MMP-3) after CXCL12 stimulation. CXCL12 also significantly Keywords: chemokine; metastasis; metalloproteinase; stromal cell-derived factor-1; SDF-1 Despite the obvious importance of metastasis, this process remains incompletely understood at both the cellular and molecular levels. 1 Many factors have been implicated in the process of metastasis, but the precise mechanisms for the directional migration of malignant cells into different organs is unknown. [2][3][4] In this regard, chemokines are a super family of small, cytokine-like proteins that inducethrough G-protein-coupled receptor and cytoskeletal rearrangement-the adhesion of neoplastic cells or leukocytes to endothelial cells as well as the directional migration of cancer cells. 5,6 The ability of neoplastic cells to penetrate the basement membrane and then invade the interstitial stroma to initiate the metastatic process is largely mediated by proteolysis. Many proteinases are capable of degrading extracellular matrix (ECM) components, but matrix metalloproteinases (MMPs) appear to be particularly important for matrix degradation. 6 These proteolytic enzymes are involved in connective tissue remodeling as well as in embryonic growth, ovulation, wound healing and menstruation. 7,8 Moreover, abnormal production of these proteinases is implicated in a number of pathological conditions. 9 It has been shown that CXCL12-CXCR4 interactions may play a role in the metastasis of prostate cancer to bone. 10 However, these interactions alone do not explain the metastasis pattern of prostate cancer or the potential for neoplastic prostate cells to migrate and invade other tissues. We have tested the hypothesis that prostate carcinomas use CXCR4-

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Section: Cxcr4-mediated Pca Migration and Invasionmentioning

confidence: 99%

CXCL12–CXCR4 interactions modulate prostate cancer cell migration, metalloproteinase expression and invasion

Singh

Grizzle

et al. 2004

Laboratory Investigation

213

187

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“…[23][24][25] In situ hybridization was performed on 5-mm sections as described in detail 26 to confirm immunohistochemical findings. Sections were hybridized with 35 S-labeled probes (3 Â 10 4 c.p.m./ml of hybridization buffer) at 501C for at least 18 h in a humidified chamber.…”

Section: In Situ Hybridizationmentioning

confidence: 99%

Transformation-specific matrix metalloproteinases, MMP-7 and MMP-13, are present in epithelial cells of keratoacanthomas

et al. 2006

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Keratoacanthomas are rapidly growing hyperproliferative skin tumors that may clinically or histologically be difficult to distinguish from well-differentiated squamous cell cancers (SCCs). UV light, trauma, and immune suppression represent their etiological factors. As matrix metalloproteinases (MMPs) are implicated at all stages of tumorigenesis, we investigated the expression profile of several cancer-related MMPs to find markers that would differentiate keratoacanthomas from SCCs and shed light to the pathobiology of keratoacanthoma. Samples from 31 keratoacanthomas and 15 grade I SCCs were studied using immunohistochemistry for MMP-2, -7, -8, -9, -10, -13, and -19 and p16 and laminin-5c2 chain. In situ hybridization for MMP-7, -10, and -13 was performed in a subset of tumors. Keratinocytes with atypia, presence of neovascularization, and composition of the inflammatory infiltrate were graded from hematoxylin-eosin stainings. MMP-7 was present in the epithelium of 4/31 keratoacanthomas and 9/15 SCCs, MMP-8 in 3/30 keratoacanthomas and 0/15 SCCs, but MMP-13 in 16/31 keratoacanthomas and 10/15 SCCs, and MMP-10 in 28/31 keratoacanthomas and all cancers. MMP-9 was detected in the epithelium in 5/31 keratoacanthomas and 8/15 SCCs, whereas MMP-2 was only present in fibroblasts in both tumors. MMP-19 was upregulated in proliferating epithelium of keratoacanthomas as was p16. Cytoplasmic laminin-5c2 was particularly abundant in keratinocytes at the pushing border of MMP-13-positive keratoacanthomas. We conclude that although some MMPs (MMP-10 and -13) are abundantly expressed in keratoacanthomas, the presence of MMP-7 and -9 in their epithelial pushing border is rare and should raise suspicion of SCC. Further, the loss of MMP-19 and p16 could aid in making the differential diagnosis between well-differentiated SCC and keratoacanthoma. Frequent expression of the transformationspecific MMP-13 in keratoacanthomas suggests that they are not benign tumors but incomplete SCCs.

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“…Hydrogels have been particularly prevalent model systems, as they have material properties that resemble natural extracellular matrices (ECMs), and their cell-interactive properties can be readily adapted to address a particular hypothesis. Therefore, natural and synthetic hydrogels have been used to gain fundamental insights into virtually all aspects of cell behavior, including cell adhesion [4], migration [5], and differentiated function [6,7]. A broad conclusion of these previous studies is that cell behavior in a 3-D context is strongly dependent on local ECM cues, particularly cell adhesion ligands, soluble or immobilized growth factors, mechanical properties, and degradability.…”

Section: Introductionmentioning

confidence: 99%

An adaptable hydrogel array format for 3-dimensional cell culture and analysis

et al. 2008

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Hydrogels have been commonly used as model systems for 3-dimensional (3-D) cell biology, as they have material properties that resemble natural extracellular matrices (ECMs), and their cellinteractive properties can be readily adapted in order to address a particular hypothesis. Natural and synthetic hydrogels have been used to gain fundamental insights into virtually all aspects of cell behavior, including cell adhesion, migration, and differentiated function. However, cell responses to complex 3-D environments are difficult to adequately explore due to the large number of variables that must be controlled simultaneously. Here we describe an adaptable, automated approach for 3-D cell culture within hydrogel arrays. Our initial results demonstrate that the hydrogel network chemistry (both natural and synthetic), cell type, cell density, cell adhesion ligand density, and degradability within each array spot can be systematically varied to screen for environments that promote cell viability in a 3-D context. In a testbed application we then demonstrate that a hydrogel array format can be used to identify environments that promote viability of HL-1 cardiomyocytes, a cell line that has not been cultured previously in 3-D hydrogel matrices. Results demonstrate that the fibronectin-derived cell adhesion ligand RGDSP improves HL-1 viability in a dose-dependent manner, and that the effect of RGDSP is particularly pronounced in degrading hydrogel arrays. Importantly, in the presence of 70µM RGDSP, HL-1 cardiomyocyte viability does not decrease even after 7 days of culture in PEG hydrogels. Taken together, our results indicate that the adaptable, array-based format developed in this study may be useful as an enhanced throughput platform for 3-D culture of a variety of cell types.

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Distinct Populations of Stromal Cells Express Collagenase-3 (MMP-13) and Collagenase-1 (MMP-1) in Chronic Ulcers but Not in Normally Healing Wounds

Cited by 244 publications

References 26 publications

CXCL12–CXCR4 interactions modulate prostate cancer cell migration, metalloproteinase expression and invasion

CXCL12–CXCR4 interactions modulate prostate cancer cell migration, metalloproteinase expression and invasion

Transformation-specific matrix metalloproteinases, MMP-7 and MMP-13, are present in epithelial cells of keratoacanthomas

An adaptable hydrogel array format for 3-dimensional cell culture and analysis

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