Expression of metalloproteinases (MMP-2 and MMP-9) in basal-cell carcinoma

Goździalska, Anna; Wojas‐Pelc, Anna; Drąg, Jagoda; Brzewski, Paweł; Jaśkiewicz, Jerzy; Pastuszczak, Maciej

doi:10.1007/s11033-016-4040-9

Cited by 23 publications

(21 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a recent study, expression profiling of BCCs showed an increase in ECM remodeling proteins including MMP-1, -3, -8, -9, and Cathepsin-K indicating the important role played by these enzymes in cancer progression (Ciazynska et al, 2018). In organ culture models of BCC the increased expression of MMP-2 and MMP-9 correlates with degradation of collagen-I and -IV at the tumor front (Goździalska et al, 2016). Likewise, the expression of ADAM-10, -12, and -17 was specifically observed in deep invasion area of BCC biopsies and correlated with the loss of collagen-XVII (Oh et al, 2009).…”

Section: Skin Diseasesmentioning

confidence: 99%

Unraveling the ECM-Immune Cell Crosstalk in Skin Diseases

Bhattacharjee

Ayyangar

Kurbet

et al. 2019

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The extracellular matrix (ECM) is a complex network of proteins and proteoglycans secreted by keratinocytes, fibroblasts and immune cells. The function of the skin ECM has expanded from being a scaffold that provides structural integrity, to a more dynamic entity that is constantly remodeled to maintain tissue homeostasis. The ECM functions as ligands for cell surface receptors such as integrins, dystroglycans, and toll-like receptors (TLRs) and regulate cellular signaling and immune cell dynamics. The ECM also acts as a sink for growth factors and cytokines, providing critical cues during epithelial morphogenesis. Dysregulation in the organization and deposition of ECMs lead to a plethora of pathophysiological conditions that are exacerbated by aberrant ECM-immune cell interactions. In this review, we focus on the interplay between ECM and immune cells in the context of skin diseases and also discuss state of the art therapies that target the key molecular players involved.

show abstract

Section: Skin Diseasesmentioning

confidence: 99%

Unraveling the ECM-Immune Cell Crosstalk in Skin Diseases

Bhattacharjee

Ayyangar

Kurbet

et al. 2019

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…MMPs are associated with tumor invasion and metastasis by degradation of the extracellular matrix. MMP2 and MMP9 degrade collagen IV, and the levels of MMP2 and MMP9 mRNA are significantly higher in nodular and infiltrative BCCs compared with normal adjacent tissue (37). In addition, MMP9 expression was significantly higher in infiltrative compared with nodular tumors.…”

Section: Discussionmentioning

confidence: 92%

A Novel Mechanism for Activation of GLI1 by Nuclear SMO That Escapes Anti-SMO Inhibitors

et al. 2018

View full text Add to dashboard Cite

Small-molecule inhibitors of the Hedgehog (HH) pathway receptor Smoothened (SMO) have been effective in treating some patients with basal cell carcinoma (BCC), where the HH pathway is often activated, but many patients respond poorly. In this study, we report the results of investigations on PTCH1 signaling in the HH pathway that suggest why most patients with BCC respond poorly to SMO inhibitors. In immortalized human keratinocytes, PTCH1 silencing led to the generation of a compact, holoclone-like morphology with increased expression of SMO and the downstream HH pathway transcription factor GLI1. Notably, although siRNA silencing of SMO in PTCH1-silenced cells was sufficient to suppress GLI1 activity, this effect was not phenocopied by pharmacologic inhibition of SMO, suggesting the presence of a second undefined pathway through which SMO can induce GLI1. Consistent with this possibility, we observed increased nuclear localization of SMO in PTCH1-silenced cells as mediated by a putative SMO nuclear/nucleolar localization signal [N(o)LS]. Mutational inactivation of the N(o)LS ablated this increase and suppressed GLI1 induction. Immunohistologic analysis of human and mouse BCC confirmed evidence of nuclear SMO, although the pattern was heterogeneous between tumors. In PTCH1-silenced cells, >80% of the genes found to be differentially expressed were unaffected by SMO inhibitors, including the putative BCC driver gene CXCL11. Our results demonstrate how PTCH1 loss results in aberrant regulation of SMO-independent mechanisms important for BCC biology and highlights a novel nuclear mechanism of SMO-GLI1 signaling that is unresponsive to SMO inhibitors. This study describes novel noncanonical Hedgehog signaling, where SMO enters the nucleus to activate GLI1, a mode that is unaffected by SMO inhibitors, thus prompting re-evaluation of current BCC treatment as well as new potential therapies targeting nuclear SMO. .

show abstract

“…[78,82] No difference in MMP-2 expression has been noted between different subtypes of BCC. [110] Expression of MMP-3 at mRNA and protein level is elevated in BCC tumors compared to unaffected tissue. [89,111] MMP-3 is expressed mainly by stromal fibroblasts and infrequently in sclerosing cancer islands.…”

Section: Mmps In Basal Cell Carcinomamentioning

confidence: 98%

Matrix metalloproteinases in keratinocyte carcinomas

Riihilä

Nissinen

Kähäri

2020

Experimental Dermatology

View full text Add to dashboard Cite

Cutaneous malignancies are the most common cancers worldwide, and their incidence is increasing globally causing mortality in ageing population. Non-melanoma skin cancers (NMSC) are classified to keratinocyte-derived basal cell carcinoma (BCC), and cutaneous squamous cell carcinoma (cSCC), which are the most common cutaneous malignancies and more than a third of patients develop multiple tumors. [1-3] Other types of non-melanoma skin cancer, including Merkel cell carcinoma, adnexal tumors and sarcomas, are less common and differ in their cell type, behaviour and epidemiology from keratinocyte carcinomas (KC). [1] Therefore, KC has become the

show abstract

Expression of metalloproteinases (MMP-2 and MMP-9) in basal-cell carcinoma

Cited by 23 publications

References 53 publications

Unraveling the ECM-Immune Cell Crosstalk in Skin Diseases

Unraveling the ECM-Immune Cell Crosstalk in Skin Diseases

A Novel Mechanism for Activation of GLI1 by Nuclear SMO That Escapes Anti-SMO Inhibitors

Matrix metalloproteinases in keratinocyte carcinomas

Contact Info

Product

Resources

About