Increased Glycosaminoglycans Production in Sclerosing Basal Cell Carcinoma-Derived Fibroblasts and Stimulation of Normal Skin Fibroblast Glycosaminoglycans Production by a Cytokine-Derived from Sclerosing Basal Cell Carcinoma

Abstract

Sclerosing basal cell carcinoma (S-BCC) is characterized by an abundant stroma. There is evidence that some tumor cells secrete cytokines that are mitogenic for stromal fibroblasts (FBs). From this study we report increased glycosaminoglycan (GAG) production by cultures of S-BCC FBs in comparison to cultures of nodular BCC (N-BCC) FBs and normal skin FBs. GAG production was measured by cetylpyridinium chloride precipitation of incorporated [3H]-glucosamine. The sclerosing BCC FBs demonstrated a significant increase in production of GAG over control FBs (P <.001) and over N-BCC FBs (P<.001). Values reported as a mean percentage +/- SEM for GAG production by S-BCC over control normal skin FBs are 359+/-28 and over N-BCC FBs are 266+/-27. In additional experiments, cell extract dilutions from S-BCC tumor, normal dermis, and normal epidermis were incubated with cultures of normal skin FBs. S-BCC-conditioned media was also incubated with normal FBs and GAG production was measured. For both S-BCC extracts and conditioned media, a dose response curve was established showing increased GAG production by normal FBs in relation to increasing the concentration of S-BCC extract or conditioned media. When S-BCC extract was added to normal FBs there was increased GAG production in comparison to normal FBs incubated with dermal or epidermal extracts (P<.001) for both. Two growth factors, transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF), already known to be mitogenic for FBs, were incubated with N-BCC and normal FBs in an effort to elucidate the potential cytokine(s) released by S-BCC, causing increased GAG production by surrounding FBs. Neither of these cytokines proved to be effective in promoting a significant increase in GAG production. Our findings support the hypothesis that BCCs release factors that alter stromal FB production of GAG.

Skin Retraction As a Marker for Aggressive Basal Cell Carcinoma

“…The clinical appearance of our patient's lesion resembled the skin dimpling or retraction that can be seen overlying some breast cancers and to some extent mimics the appearance of a pursestring wound closure. Sclerosing BCC tumor cells have been shown to secrete cytokines, such as transforming growth factor beta, that promote proliferation of fibroblasts and production of glycosaminoglycans . Aggressive BCC tumor cell subtypes have high expression of a variety of collagenases and matrix metalloproteinases, which facilitate tumor invasion and spread through the dermis .…”

Nodular basal cell carcinoma is associated with increased hyaluronan homeostasis

“…48 Furthermore, Moy et al, demonstrated that fibroblasts from nodular and sclerosing BCC, produce more GAGs, when compared with normal fibroblasts. 49 The authors suggested that cells from superficial and nodular BCC types are capable of producing cytokines which alter stromal fibroblast production of GAGs and stimulate collagenase synthesis. 49 In addition, Bertheim et al, demonstrated that in nodular BCC, HA staining of the tumour strands was weak to moderate, denoting increased proliferative activity.…”

“…49 The authors suggested that cells from superficial and nodular BCC types are capable of producing cytokines which alter stromal fibroblast production of GAGs and stimulate collagenase synthesis. 49 In addition, Bertheim et al, demonstrated that in nodular BCC, HA staining of the tumour strands was weak to moderate, denoting increased proliferative activity. They also reported that the differentiated surrounding tumour stroma stained strongly for HA.…”

A case of syringoid eccrine carcinoma with circumscribed abundant stroma

“…2,3 Further clinical and experimental evaluation may elucidate the sclerosing mechanism, although the causative factor may differ in each malignancy. On the other hand, the resultant stroma formation can have impacts on mitogenic and motogenic activities of tumour cells.…”

“…1 EAC was first described by Darrier. 2 Subsequently, Ackerman, basing on the histopathologic aspects, distinguished between superficial and deep forms. 3 Some authors considered EAC as a hypersensitivity reaction that may be associated with underlying diseases.…”