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

Abstract

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.

Keywords: cancer; collagen XVII; ectodomain shedding; literature review; skin cancer.

Figure 1

Schematic diagram of the molecular organization of a hemidesmosorne at the dermoepidermal basement membrane. The intracellular plaque is associated with transmembrane adhesion molecules, including integrins and transmembrane type XVII collagen (BP 180). It contains plectin and BP 230 (BPAG1). Type XVII collagen regulates expression and function of laminin- 332. The interaction between laminin-332 and the extracellular portions of a6β4 integrin stabilizes hemidesmosomes. This interaction is essential for hemidesmosome formation and epithelial adhesion.

Figure 2

Structure of collagen XVII. The intracellular domain (lCD; aa 1–456), transmembrane domain (TD; aa 457–489), and extracellular domain (ECD; aa 490–1497). The ECD includ es the NC16A domain (aa 490–562). The ICD lies in the outer plaque of the HD and the ECD spans the lamina Iucida, extends to the lamina densa, and loops back into the lamina Iucida.