Chondroitin Sulfate Proteoglycan 4 as a Marker for Aggressive Squamous Cell Carcinoma

Abstract

Chondroitin sulfate (CS) proteoglycan 4 (CSPG4) is a cell surface proteoglycan that is currently under investigation as a marker of cancer malignancy, and as a potential target of anticancer drug treatment. CSPG4 acts as a driver of tumourigenesis by regulating turnover of the extracellular matrix (ECM) to promote tumour cell invasion, migration as well as inflammation and angiogenesis. While CSPG4 has been widely studied in certain malignancies, such as melanoma, evidence is emerging from global gene expression studies, which suggests a role for CSPG4 in squamous cell carcinoma (SCC). While relatively treatable, lack of widely agreed upon diagnostic markers for SCCs is problematic, especially for clinicians managing certain patients, including those who are aged or infirm, as well as those with underlying conditions such as epidermolysis bullosa (EB), for which a delayed diagnosis is likely lethal. In this review, we have discussed the structure of CSPG4, and quantitatively analysed CSPG4 expression in the tissues and pathologies where it has been identified to determine the usefulness of CSPG4 expression as a diagnostic marker and therapeutic target in management of malignant SCC.

Hawthorn Proanthocyanidin Extract Inhibits Colorectal Carcinoma Metastasis by Targeting the Epithelial-Mesenchymal Transition Process and Wnt/β-Catenin Signaling Pathway

“…Proteoglycans play key roles in regulating cell signal transduction and migration through interactions with extracellular ligands, growth factor receptors, ECM components, intracellular enzymes, and structural proteins [50]. In cancer, various proteoglycans influence tumor cell invasion, migration, and angiogenesis by regulating EMT, thereby affecting the initiation and progression of tumors [51][52][53]. In CRC, MMPs, particularly MMP-2 and MMP-9, are implicated in EMT, playing a role in the degradation of type IV collagen in the basement membrane and increasing tumor invasiveness [49].…”

Molecular and Histopathological Characterization of Metastatic Cutaneous Squamous Cell Carcinomas: A Case–Control Study

“…The activation of this pathway has already been demonstrated in head and neck SCCs [ 49 ]. Interestingly, CSPG4 has also been found among upregulated genes; CSPG4 has already been proposed as a putative diagnostic marker in aggressive forms of SCC with an active role in cancer progression [ 50 ]. Moreover, specific blocking antibodies against CSPG4 have been described to reduce tumor growth and metastasis in vivo [ 51 ].…”

Biomarker Discovery in Rare Malignancies: Development of a miRNA Signature for RDEB-cSCC

“…Although there is an eminent need for minimally invasive diagnostic tests to support physicians in their effort to detect aggressive RDEB tumors at an early stage, to date there are still only very few studies on potential diagnostic markers. Most of them are at an early observational stage showing a tendency of RDEB-cSCC to present altered levels of certain molecules such as complement associated serine proteases and aberrant expression of a specific cell surface proteoglycan in RDEB-cSCC [ 53 , 54 ]. However, initial studies, including the one presented here, are now elucidating the potential of tumor-associated molecules secreted and protected in microvesicles.…”