Matrix metalloproteinase‐26 is present more frequently in squamous cell carcinomas of immunosuppressed compared with immunocompetent patients

Kuivanen, Tiina; Jeskanen, Leila; Kyllönen, L.; Isaka, Keiichi; Saarialho–Kere, Ulpu

doi:10.1111/j.1600-0560.2009.01188.x

Cited by 11 publications

(24 citation statements)

References 32 publications

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“…A transforming growth factor (TGF)‐β1 enriched tumor environment coupled with amplified EGFR levels or signalling correlates with increased expression of MMP‐10 (36). Our recent results (13) on the higher number of MMP‐9 positive macrophages in SCCs of non‐IS compared with IS patients, and the presence of angiogenesis‐promoting MMP‐9 positive neutrophils in SCCs of tranplanted patients, further emphasize the role of stromal cells in the biological behaviour of skin tumors. Moreover, in our recent study comparing basal cell carcinomas (BCCs) of IS and control patients, MMP‐10 expression was detected in BCC tumor cells and stromal fibroblasts and macrophages as well (37) but no essential differences between the two groups studied were noted.…”

Section: Discussionmentioning

confidence: 57%

“…Some MMPs, such as MMPs-8, -12 and -26, have an anti-tumor effect depending on the stage of cancer progression (12). We have recently shown that among classical cancer-related MMPs, overexpression of MMP-1, -7, -8 and -13 does not explain the more aggressive behaviour of SCCs in renal transplant recipients nor diminished expression of tissue inhibitors of MMPS, TIMP-1 or TIMP-3 (13).…”

Section: Introductionmentioning

confidence: 99%

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MMP‐10 (Stromelysin‐2) and MMP‐21 in human and murine squamous cell cancer

Boyd

Virolainen

Pärssinen

et al. 2009

Experimental Dermatology

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The squamous cell cancers (SCC) of renal transplant recipients are more aggressive and metastasize earlier than those of the non-immunocompromised population. Matrix metalloproteinases (MMPs) have a central role in tumor initiation, invasion and metastasis. Our aim was to compare the expression of MMPs-10, -12 and -21 in SCCs from immunosuppressed (IS) and control patients and the contribution of MMPs-10 and -21 to SCC development in the FVB/N-Tg(KRT5-Nfkbia)3Rto mouse line. Immunohistochemical analysis of 25 matched pairs of SCCs, nine of Bowen's disease and timed back skin biopsies of mice with selective inhibition of Rel/NF-kappaB signalling were performed. Semiquantitatively assessed stromal MMP-10 expression was higher (P = 0.009) in the control group when compared with IS patients. Tumor cell-derived MMP-10, -12 and -21 expression did not differ between the groups but stromal fibroblasts of the control SCCs tended to express MMP-21 more abundantly. MMP-10 expression was observed already in Bowen's disease while MMP-21 was absent. MMP-10 and -21 were present in inflammatory or stromal cells in ageing mice while dysplastic keratinocytes and invasive cancer were negative. Our results suggest that MMP-10 may be important in the initial stages of SCC progression and induced in the stroma relating to the general host-response reaction to skin cancer. MMP-21 does not associate with invasion of SCC but may be involved in keratinocyte differentiation.

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Section: Discussionmentioning

confidence: 57%

Section: Introductionmentioning

confidence: 99%

MMP‐10 (Stromelysin‐2) and MMP‐21 in human and murine squamous cell cancer

Boyd

Virolainen

Pärssinen

et al. 2009

Experimental Dermatology

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“…We have recently studied the role of several novel MMPs, such as MMP-21 [17], MMP-26 [18], and MMP-28 [19] in skin cancer. The aim of the present study was to elucidate the role of more novel MMPs in the biological behavior of MCC in vivo and in culture, correlating the findings with tumor size and presence of metastatic lymph nodes.…”

Section: Introductionmentioning

confidence: 99%

“…. Polyclonal antibodies raised by us against a synthetic peptide were used for MMP-21[22], for MMP-26 (1:120, a gift from Prof. K. Isaka, Tokyo Medical University)[18], Neutrophils, macrophages, and plasma cells were histologically identified from immunostained and corresponding hematoxylin-eosin stained sections by an experienced pathologist (T. B.…”

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confidence: 99%

Expression of MMP-10, MMP-21, MMP-26, and MMP-28 in Merkel cell carcinoma

et al. 2009

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Merkel cell carcinoma (MCC) is an aggressive cutaneous tumor with poor outcome and increasing incidence. We examined by immunohistochemistry the expression of three novel matrix metalloproteinases (MMPs)-MMP-21, MMP-26, and MMP-28-in 44 primary MCC tumors and six lymph node metastases while MMP-10 served as a positive control. Their mRNA expression was also studied in the UISO MCC cell line basally and after various stimulations using quantitative real-time PCR. MMP-28 was observed in tumor cells of 15/44 samples especially in tumors <2 cm in diameter (p = 0.015) while 21/44 specimens showed MMP-28 in the tumor stroma. Expression of MMP-21 was demonstrated in tumor cells of 13/43 samples. MMP-26, instead, was positive in stromal cells (17/44) and its expression associated with tumors >or=2 cm in diameter (p = 0.006). Stromal expression of MMP-10 was the most frequent finding of the studied samples (31/44), but MMP-10 was detected also in tumor cells (17/44). Most of the metastatic lymph nodes expressed MMP-10 and MMP-26. MMP-10, MMP-21, and MMP-28 mRNAs were basally expressed by the UISO cells, and the corresponding proteins were detectable by immunostaining of cultured cells. IFN-alpha and TNF-alpha downregulated MMP-21 and MMP-28 expression. Our results suggest that novel MMPs may have a role in MCC pathogenesis: especially that MMP-26 expression in stroma is associated with larger tumors with poor prognosis. Expression of MMP-21 and MMP-28 seems to associate with the tumors of lesser malignant potential. We also confirm the previous finding on the role of MMP-10 in MCC pathogenesis.

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“…times more frequently than BCC in OTR, while the reverse is noted in ICP [4]. Significant morbidity and mortality are associated with cSCC in OTR resulting from their multiplicity and their potentially aggressive clinical outcome.…”

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confidence: 99%