The dysfunction of BP180/collagen XVII in keratinocytes promotes melanoma progression

Hwang, Bin-Jin; Zhang, Yang; Brozowski, Jaime M.; Liu, Zhen; Burette, Susan; Lough, Kendall J.; Smith, Christof C.; Shan, Yue; Chen, J.; Li, Ning; Williams, Scott; Su, Maureen A.; Thomas, Nancy E.; Li, Zhi

doi:10.1038/s41388-019-0961-9

Cited by 14 publications

(16 citation statements)

References 56 publications

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Section: Neural Crest Tumorsmentioning

confidence: 76%

“…In vivo models using skin specific-NC16A dysfunctional mice with B16 melanoma cells support the regulatory role of keratinocyte collagen XVII on melanoma tumorigenesis (61,62). When compared to the controls, the experimental models showed increased levels of tumor volume and lymphatic metastasis (62). Collagen XVII dysfunction results in immediate inflammation, previously identified as a hallmark for cancer, through the influx of chemokines which further recruit myeloid derived suppressor cells (MDSCs) (61,63).…”

Section: Neural Crest Tumorsmentioning

confidence: 78%

“…Collagen XVII dysfunction results in immediate inflammation, previously identified as a hallmark for cancer, through the influx of chemokines which further recruit myeloid derived suppressor cells (MDSCs) (61,63). Decreasing the levels of MDSCs through treatment with specific antibodies resulted in the reduction of tumor volume, and the rate of metastatic development, demonstrating the role collagen XVII plays in curbing tumor invasion via regulation of MDSC infiltration (62). As some studies have noted an association between bullous pemphigoid and melanoma, particularly after immunotherapy, this remains a potentially relevant interaction (64,65).…”

Section: Neural Crest Tumorsmentioning

confidence: 98%

“…Collagen XVII assumes various roles in epithelial biology including but not limited to cell differentiation, cell migration, and skin inflammation. In a variety of tumors, genetic aberrations in COL17A1, full-length collagen XVII overexpression, or the accumulation of its proteolytic components have been linked to increased invasiveness of tumors (52,62,67,69). For example, ectodomain shedding of COL XVII is catalyzed by ADAM9 and ADAM10 (27,36,86), and ectodomain release promotes tumor invasion (59).…”

Section: Future Perspectives: Collagen XVII and Cancer Treatmentmentioning

confidence: 99%

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The Role of Collagen XVII in Cancer: Squamous Cell Carcinoma and Beyond

et al. 2020

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Alterations in the extracellular matrix (ECM) likely facilitate the first steps of cancer cell metastasis and supports tumor progression. Recent data has demonstrated that alterations in collagen XVII (BP180), a transmembrane protein and structural component of the ECM, can have profound effects on cancer invasiveness. Collagen XVII is a homotrimer of three α1 (XVII) chains. Its intracellular domain contains binding sites for plectin, integrin β4, and BP230, while the extracellular domain facilitates interactions between the cell and the ECM. Collagen XVII and its shed ectodomain have been implicated in cell motility and adhesion and are believed to promote tumor development and invasion. A strong association of collagen XVII ectodomain shedding and tumor invasiveness occurs in squamous cell carcinoma (SCC). Aberrant expression of collagen XVII has been reported in many epithelial cancers, ranging from squamous cell carcinoma to colon, pancreatic, mammary, and ovarian carcinoma. Thus, in this review, we focus on collagen XVII's role in neoplasia and tumorigenesis. Lastly, we discuss the importance of targeting collagen XVII and its ectodomain shedding as a novel strategy to curb tumor growth and reduce metastatic potential.

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Section: Neural Crest Tumorsmentioning

confidence: 76%

Section: Neural Crest Tumorsmentioning

confidence: 78%

Section: Neural Crest Tumorsmentioning

confidence: 98%

Section: Future Perspectives: Collagen XVII and Cancer Treatmentmentioning

confidence: 99%

See 2 more Smart Citations

The Role of Collagen XVII in Cancer: Squamous Cell Carcinoma and Beyond

et al. 2020

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“…Moreover, basal keratinocytes express BP180/collagen XVII, which is a cell-matrix adhesion protein related to different types of skin cancers, including melanoma [ 48 , 49 ]. Hwang et al showed that keratinocytes derived from BP180-deficient mice exhibited the upregulation of CXCL1 expression compared to control animals, in which cytokine acts as a chemoattractant for myeloid-derived suppressor cells (MDSCs).…”

Section: Keratinocytesmentioning

confidence: 99%

Stromal Cells Present in the Melanoma Niche Affect Tumor Invasiveness and Its Resistance to Therapy

Mazurkiewicz

Simiczyjew

Dratkiewicz

et al. 2021

IJMS

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Malignant melanoma is a highly metastatic type of cancer, which arises frequently from transformed pigment cells and melanocytes as a result of long-term UV radiation exposure. In recent years, the incidence of newly diagnosed melanoma patients reached 5% of all cancer cases. Despite the development of novel targeted therapies directed against melanoma-specific markers, patients’ response to treatment is often weak or short-term due to a rapid acquisition of drug resistance. Among the factors affecting therapy effectiveness, elements of the tumor microenvironment play a major role. Melanoma niche encompasses adjacent cells, such as keratinocytes, cancer-associated fibroblasts (CAFs), adipocytes, and immune cells, as well as components of the extracellular matrix and tumor-specific physicochemical properties. In this review, we summarize the current knowledge concerning the influence of cancer-associated cells (keratinocytes, CAFs, adipocytes) on the process of melanomagenesis, tumor progression, invasiveness, and the emergence of drug resistance in melanoma. We also address how melanoma can alter the differentiation and activation status of cells present in the tumor microenvironment. Understanding these complex interactions between malignant and cancer-associated cells could improve the development of effective antitumor therapeutic strategies.

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Melanoma is associated with an increased risk of bullous pemphigoid: a large population-based longitudinal study

et al. 2021

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The association between bullous pemphigoid (BP) and melanoma is yet to be investigated. We aimed to assess assess the bidirectional association between BP and melanoma and to delineate the epidemiological features of patients with both diagnoses. A population-based cohort study was performed comparing BP patients (n = 3924) with age-, sex- and ethnicity-matched control subjects (n = 19,280) with regard to incident cases of melanoma. A case–control design was additionally adopted to estimate the risk of BP in individuals with a preexisting diagnosis of melanoma. The prevalence of preexisting melanoma was higher in patients with BP than in control subjects (1.5% vs. 1.0%, respectively; P = 0.004). A history of melanoma confers a 50% increase in the risk of subsequent BP (OR 1.53; 95% CI 1.14–2.06). This risk was higher among males (OR 1.66; 95% CI 1.09–2.54) and individuals older than 80 years (OR 1.63; 95% CI 1.11–2.38), and persisted after adjustment for multiple putative confounders including PD-1/PDL-1 antagonists (adjusted OR 1.53; 95% CI 1.14–2.06). Conversely, the risk of melanoma among patients with BP was slightly elevated, but did not reach the level of statistical significance (adjusted HR 1.13; 95% CI 0.73–1.74). Patients with a dual diagnosis of BP and melanoma were older at the onset of BP and had lower body mass index. A history of melanoma is associated with a 50% increase in the incidence of subsequent BP. Physicians managing patients with both conditions should be aware of this association. Further research is warranted to reveal the underlying mechanism of these findings.

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The dysfunction of BP180/collagen XVII in keratinocytes promotes melanoma progression

Abstract: The current affiliation of Zhen Liu is the Guangdong Center for Adverse Drug Reactions of Monitoring, Guangzhou, PRC. The current affiliation of Maureen Su is, the

Cited by 14 publications

References 56 publications

The Role of Collagen XVII in Cancer: Squamous Cell Carcinoma and Beyond

The Role of Collagen XVII in Cancer: Squamous Cell Carcinoma and Beyond

Stromal Cells Present in the Melanoma Niche Affect Tumor Invasiveness and Its Resistance to Therapy

Melanoma is associated with an increased risk of bullous pemphigoid: a large population-based longitudinal study

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