Dermatology Medical News about matrix metalloprotease, tumor progression, angiogenesis, tumor-stroma interaction

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Distinct progression-associated expression of tumor and stromal MMPs in HaCaT skin SCCs correlates with onset of invasion
International Journal of Cancer, 07/21/09

Vosseler S et al. - In a study to determine whether distinct progression-associated expression of tumor and stromal matrix metalloproteinases (MMPs) in HaCaT skin squamous cell carcinoma (SCC) correlates with onset of invasion, these data demonstrate a complex cooperation of distinct tumor and stroma-derived MMPs in the establishment of malignant tumors and provide the basis for a more specific use of highly selective MMP inhibitors during distinct stages of tumor progression.

Methods

HaCaT-keratinocyte clones representing distinct stages in skin SCC progression were used.

Results

Although MMP-9-positive leukocytes are present in benign and malignant tumor transplants at the onset of stromal activation and angiogenesis, mRNA expression of stroma-derived MMP-9 as well as MMP-2, -13 and -14 is exclusively found in enhanced malignant tumor transplants.
Their expression initiates with onset of invasion, whereas being absent in early noninvasive stages of malignant transplants.
High expression of tumor-derived MMP-1, -2 and -14 contributes to malignant and invasive tumor growth.
Stroma-derived MMP-3 is exclusively restricted to very late-stage invasive and malignant transplants.
Functional contribution of these proteases to invasive growth is supported by the gelatinolytic activity in the tumor transplants that again initiates with the onset of invasive growth suggesting a crucial role of MMP-2, -9, -13 and -14 for establishment of a reactive stroma that promotes tumor invasion.

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