Fibronectin, Laminin, Type IV Collagen Distribution, and Myofibroblastic Stromal Reaction in Aggressive and Nonaggressive Basal Cell Carcinoma

Rosa, Gaetano De; Barra, Enrica; Guarino, Marcello; Staibano, Stefania; Donofrio, Vittoria; Boscaino, Amedeo

doi:10.1097/00000372-199406000-00006

Cited by 42 publications

(25 citation statements)

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“…As supported also by the presented immunohistochemical SMA data, BCC can be accompanied by a striking stromal reaction, which seems to be associated with aggressiveness (De Rosa et al 1994). Because in BCC Snail-positive stromal cells were not detected, we would like to suggest that a linked SMA and Snail positivity is a speciWc phenomenon of stroma formation in tumours with metastatic potential.…”

Section: Immunohistochemical Snail Expression In Oscc Is a Phenomenonsupporting

confidence: 56%

Expression of Snail is associated with myofibroblast phenotype development in oral squamous cell carcinoma

Franz

Spiegel

Umbreit

et al. 2009

Histochem Cell Biol

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Snail is a regulator of epithelial-mesenchymal transition (EMT) and considered crucial to carcinoma metastasis, myofibroblast transdifferentiation, and fibroblast activation. To investigate the role of Snail in oral squamous cell carcinoma (OSCC), its immunohistochemical expression was analysed in 129 OSCC samples and correlated to nodal metastasis, histological grade, E-cadherin, and alpha smooth-muscle-actin (alpha SMA). The results were compared to findings in 23 basal cell carcinomas (BCC). Additionally, the influence of TGF beta 1 and EGF on Snail, E-cadherin, vimentin, and alpha SMA expression was analysed in two OSCC cell lines. As a result, Snail-positive cells were mainly found in the stroma of the OSCC invasive front without statistically significant correlation to histological grade or nodal metastasis. Snail was co-localised to alpha SMA but not to E-cadherin or cytokeratin and showed a significant correlation to the loss of membranous E-cadherin. All BCCs were Snail negative. In OSCC culture, the growth-factor-mediated EMT-like phenomenon was accompanied by alpha SMA down-regulation. In summary, Snail expression in OSCC is a stromal phenomenon associated with the myofibroblast phenotype and not related to growth-factor-mediated transdifferentiation of the carcinoma cells themselves. Consequently, Snail immunohistochemistry cannot contribute to the prediction of the metastatic potential. Furthermore, stromal Snail expression is suggested to be the result of mutual paracrine interaction of fibro-/myofibroblasts and dedifferentiated carcinoma cells leading to the generation of a special type of carcinoma-associated fibroblasts.

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Section: Immunohistochemical Snail Expression In Oscc Is a Phenomenonsupporting

confidence: 56%

Expression of Snail is associated with myofibroblast phenotype development in oral squamous cell carcinoma

Franz

Spiegel

Umbreit

et al. 2009

Histochem Cell Biol

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“…However, the authors cannot correlate increments of Erk1/2 phosphorylation with fibroblasts activation because they did not observe morphological or proliferation changes and incremented vimentin expression. 22 The authors hypothesize that paracrine and autocrine signalization may exist in the stroma of BCC tumors probably regulating the growth and survive of the tumor and that some degree of autocrine signalization still remains in cultures of BCC fibroblasts. Further study of stroma fibroblasts, vascular, and inflammatory cells are required to elucidate the function of stroma in BCC formation.…”

Section: Discussionmentioning

confidence: 99%

Erk1/2 Activation in Stromal Fibroblasts From Sporadic Basal Cell Carcinomas

Aguayo

Rafel

Santacana

et al. 2015

Dermatologic Surgery

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“…This substance usually comprises collagen types IV and V, laminin, fibronectin, and sulfated and nonsulfated glycosaminoglycans. [35][36][37] Collagen is the most abundant composition of the BM, and among its different types, type IV is the main structural component of the BM. Our results indicate that staining of type IV collagen and PAS demonstrate partial loss of PASpositive basement membrane in the skin lesions of Slit2-Tg mice that are at the stages of CIS and carcinoma and, similarly in wild-type mice that are at the stage of CIS ( Figure 5).…”

Section: Discussionmentioning

confidence: 99%

Slit2 promotes tumor growth and invasion in chemically induced skin carcinogenesis

Lan

et al. 2014

Laboratory Investigation

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Slit, a neuronal guidance cue, binds to Roundabout (Robo) receptors to modulate neuronal, leukocytic, and endothelial migration. Slit has been reported to have an important effect on tumor growth and metastasis. In the current study, we evaluated the role of Slit2 in skin tumor growth and invasion in mice using a two-step chemical carcinogenesis protocol. We found that Slit2 expression correlated with the loss of basement membrane in the samples of human skin squamous cell carcinoma at different stages of disease progression. Slit2-Tg mice developed significantly more skin tumors than wild-type mice. Furthermore, the skin tumors that occurred in Slit2-Tg mice were significantly larger than those in the wild-type mice 10 weeks after 7,12-dimethylbenz[a]anthracene initiation until the end of the experiment. We also found that pathological development of the wild-type mice was delayed compared with that of Slit2-Tg mice. To further investigate the mechanism of increasing tumors in Slit2-Tg mice, we analyzed the expression of 5-bromo-2 0 -deoxyuridine (BrdU) in mouse skin lesions and found that the number of BrdU-positive cells and microvessel density in skin lesions were significantly higher in Slit2-Tg mice than in wild-type mice. Histological staining of PAS and type IV collagen and the colocalization of Slit2 and type IV collagen demonstrated varying degrees of loss of the basement membrane in the skin lesions from Slit2-Tg mice that were at the stage of carcinoma in situ. However, the basement membrane was well defined in the wild-type mice. In addition, MMP2, but not MMP9, was upregulated in the skin tissue of Slit2-Tg mice. Interruption of Slit2-Robo1 signaling by the antibody R5 significantly repressed the invasive capability of the squamous cell carcinoma cell line A431. Taken together, our findings reveal that Slit2 promotes DMBA/TPA-induced skin tumorigenesis by increasing cell proliferation, microvessel density, and invasive behavior of cutaneous squamous cell carcinoma, along with loss of basement membrane, by upregulation of MMP2 expression. Skin cancer is one of the most common malignant tumors. Approximately 2 to 3 million cases of nonmelanoma skin cancer occur annually worldwide, and its incidence has been rising rapidly over the past several decades. 1 Skin cancer develops through a multistage process that includes initiation, promotion, and progression, as shown in experimental animal models. 2 The two-stage murine skin carcinogenesis model, which comprises two distinctly separate stages (initiation and promotion), is one of the most well-established in vivo models of experimental carcinogenesis. After 7, anthracene (DMBA) initiation, repeated applications of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) promote papillomas and eventually carcinomas. 3 Slit, a member of neuronal guidance cues, has been implicated to play an important role in tumor progression. 4 The Slit family consists of three members (Slit1, Slit2, and Slit3) that are expressed in the nervous system, whereas Slit...

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Fibronectin, Laminin, Type IV Collagen Distribution, and Myofibroblastic Stromal Reaction in Aggressive and Nonaggressive Basal Cell Carcinoma

Cited by 42 publications

References 0 publications

Expression of Snail is associated with myofibroblast phenotype development in oral squamous cell carcinoma

Expression of Snail is associated with myofibroblast phenotype development in oral squamous cell carcinoma

Erk1/2 Activation in Stromal Fibroblasts From Sporadic Basal Cell Carcinomas

Slit2 promotes tumor growth and invasion in chemically induced skin carcinogenesis

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