Elevated expression of MMP-13 and TIMP-1 in head and neck squamous cell carcinomas may reflect increased tumor invasiveness

Çulhacı, Nil; Metin, Kubilay; Copçu, Eray; Dikicioğlu, Emel

doi:10.1186/1471-2407-4-42

Cited by 64 publications

(58 citation statements)

References 20 publications

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“…However, it may also act as a potent gelatinase by degrading a wide variety of extracellular matrix components (30,31). MMP-13 is overexpressed in a variety of tumors from such as head and neck, laryngeal, breast, chondrosarcoma, gastric, colorectal, vulvar carcinomas and cutaneous malignant lymphoma (17,(32)(33)(34)(35)(36)(37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

Matrix Metalloproteinase-13 (MMP-13) Directly and Indirectly Promotes Tumor Angiogenesis

Kudo

Iizuka

Yoshida

et al. 2012

Journal of Biological Chemistry

120

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Background:Angiogenesis is an important step in the metastatic cascade of tumors. Results: MMP-13 itself as well as VEGF-A secretion from fibroblasts promotes angiogenesis. Indeed, MMP-13 is well correlated with blood vessel density in human cancer tissues. Conclusion: MMP-13 can be a marker for prediction of malignant behaviors and a therapeutic target in cancer. Significance: This work provides new insights regarding the role of MMP-13 in tumor angiogenesis.

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Section: Discussionmentioning

confidence: 99%

Matrix Metalloproteinase-13 (MMP-13) Directly and Indirectly Promotes Tumor Angiogenesis

Kudo

Iizuka

Yoshida

et al. 2012

Journal of Biological Chemistry

120

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“…Conversely, increased expression of both of these metalloproteinases has been detected in numerous solid tumors and has also been causally linked to tumor expansion and increased invasiveness. For example, increased MMP-9 and MMP-13 activity is associated with poor prognosis in colorectal cancer (25) and increased invasion of squamous cell carcinoma cells in vivo (2,12). Similarly, human tongue carcinoma cell invasion and tumor expansion have been linked to MMP-9 and MMP-13 catalytic activity (30).…”

Section: Downloaded Frommentioning

confidence: 99%

FOXO3a Promotes Tumor Cell Invasion through the Induction of Matrix Metalloproteinases

Störz

Döppler

Copland

et al. 2009

Molecular and Cellular Biology

143

133

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The role of the Forkhead transcription factor FOXO3a in processes that promote tumor metastasis is poorly defined. Here, we show that depletion of FOXO3a from cancer cells leads to decreased tumor size specifically due to attenuated invasive migration. During tumor progression, an increase in tumor mass is concomitant with serum deprivation prior to tumor angiogenesis. We show that nuclear retention of FOXO3a due to serum starvation results in greatly increased cancer cell invasion. Exploration of the mechanism by which FOXO3a promotes invasive migration revealed that it induces the expression of matrix metalloproteinase 9 (MMP-9) and MMP-13, both of which have been causally linked to the invasion and progression of numerous human solid tumors. Our results link Forkhead transcription factors to a previously unexplored function in cancer progression by promoting extracellular matrix degradation, allowing tumors to invade neighboring tissues and ultimately metastasize to distant organs.

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“…In particular, MMP2, MMP-9, and MMP-13 are highly expressed in OSCC compared with normal oral mucosa tissues, and their mRNA and protein levels are further increased on tumor progression (6)(7)(8). In addition, it is well established that MMP2, MMP-9, and MMP-13 are closely associated with tumor invasion and metastasis in a variety of human tumors (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

CXCR4 Promotes Oral Squamous Cell Carcinoma Migration and Invasion through Inducing Expression of MMP-9 and MMP-13 via the ERK Signaling Pathway

Helman

et al. 2011

Molecular Cancer Research

112

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The increased migration and invasion of oral squamous cell carcinoma cells are key events in the development of metastasis to the lymph nodes and distant organs. Although the chemokine receptor CXCR4 and its ligand, stromal cell-derived factor-1a, have been found to play an important role in tumor invasion, its precise role and potential underlying mechanisms remain largely unknown. In this study, we showed that knockdown of CXCR4 significantly decreased Tca8113 cells migration and invasion, accompanied with the reduction of MMP-9 and MMP-13 expression. Inhibition of ligand binding to CXCR4 by a specific antagonist TN14003, also led to reduced cancer cell migration and invasion. Because the degradation of the extracellular matrix and the basement membrane by proteases, such as matrix metalloproteinases (MMP) is critical for migration and invasion of cancer cells, we investigated the expression of several MMPs and found that the expression of functional MMP-9 and MMP-13 was selectively decreased in CXCR4 knockdown cells. More importantly, decreased cell migration and invasion of CXCR4 knockdown cells were completely rescued by exogenous expression of MMP-9 or MMP-13, indicating that the two MMPs are downstream targets of CXCR4-mediated signaling. Furthermore, we found the level of phosphorylated extracellular signal-regulated kinase (ERK) was significantly decreased in CXCR4-silenced cells, suggesting that ERK may be a potential mediator of CXCR4-regulated MMP-9 and MMP-13 expression in Tca8113 cells. Taken together, our results strongly suggest the underlying mechanism of CXCR4 promoting Tca8113 migration and invasion by regulating MMP-9 and MMP-13 expression perhaps via activation of the ERK signaling pathway. Mol Cancer Res; 9(2); 161-72. Ó2011 AACR.

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Elevated expression of MMP-13 and TIMP-1 in head and neck squamous cell carcinomas may reflect increased tumor invasiveness

Cited by 64 publications

References 20 publications

Matrix Metalloproteinase-13 (MMP-13) Directly and Indirectly Promotes Tumor Angiogenesis

Matrix Metalloproteinase-13 (MMP-13) Directly and Indirectly Promotes Tumor Angiogenesis

FOXO3a Promotes Tumor Cell Invasion through the Induction of Matrix Metalloproteinases

CXCR4 Promotes Oral Squamous Cell Carcinoma Migration and Invasion through Inducing Expression of MMP-9 and MMP-13 via the ERK Signaling Pathway

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