MMP-10 (Stromelysin-2) and MMP-21 in human and murine squamous cell cancer.
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.
Boyd
Sonja
S
Department of Pathology, Helsinki University Central Hospital and Haartman Institute, University of Helsinki, Helsinki, Finland.
Virolainen
Susanna
S
Pärssinen
Jenita
J
Skoog
Tiina
T
van Hogerlinden
Max
M
Latonen
Leena
L
Kyllönen
Lauri
L
Toftgard
Rune
R
Saarialho-Kere
Ulpu
U
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001913:Bowen's Disease / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use; D004195:Disease Models, Animal; D004727:Endothelium / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects; D008214:Lymphocytes / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D053506:Matrix Metalloproteinase 10 / Q000378:metabolism*; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism; D053505:Matrix Metalloproteinases, Secreted / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
D016572:Cyclosporine; D066246:ErbB Receptors; C471969:MMP21 protein, human; C549024:MMP21 protein, mouse; D053505:Matrix Metalloproteinases, Secreted; D053506:Matrix Metalloproteinase 10; D053508:Matrix Metalloproteinase 12