Expression of gp130 in Tumors and Inflammatory Disorders of the Skin: Formal Proof of its Identity as CD146 (MUC18, Mel-CAM)

Abstract

Two antibodies, BT14 and L101, detect a tumor-associated cell surface glycoprotein (gp130) whose properties in normal and diseased skin were assessed, and whose molecular identity was determined in this study. In normal skin, gp130 was constitutively expressed on dermal blood vessels and epidermal appendages, but not in interfollicular epidermis. Marked induction was detected within benign and malignant tumors of various origins including viral warts, basal cell carcinomas, squamous cell carcinomas, metastatic melanomas, and cutaneous T cell lymphomas. In vitro studies confirmed the general upregulation of gp130 expression in malignantly transformed cells. Surprisingly, gp130 was also induced in inflammatory skin diseases including psoriasis and allergic contact dermatitis. Halting proliferation of transformed keratinocytes through cytostatic drugs or increasing the Ca2+ concentration in the medium resulted in increased gp130 expression. In addition, overexpression of Bcl-2 led to upregulation of gp130. When the protein was purified and analyzed by peptide mass fingerprinting, we could demonstrate that it is MUC18 (Mel-CAM, CD146). Sequential immunoprecipitations and western blot analyses confirmed the identity of the antigen. Thus, both expression pattern and regulation characteristics of the now-known glycoprotein gp130 extended beyond previously published data regarding MUC18, thus shedding some new light on a supposedly well-known antigen.

Differential CD146 Expression on Circulating Versus Tissue Endothelial Cells in Rectal Cancer Patients: Implications for Circulating Endothelial and Progenitor Cells As Biomarkers for Antiangiogenic Therapy

“…This is consistent with previous results that identified CD146 expression on activated T cell subsets in healthy individuals. 14,17,18,21 Moreover, the pretreatment blood concentration of these cells was in the same range as that of CD31 bright CD45 − cells (20 to 100 cells/μL of blood 9 ), but their concentration during anti-VEGF treatment showed no significant changes, in contrast to the significant decrease of CD31 bright CD45 − cells. 5,9 The detectable expression of CD146 in endothelial cells derived from buffy coats and expanded in culture 15 may be functionally associated with cell proliferation, differentiation, formation of cell-cell junctions, and/or cytoskeletal rearrangement.…”

“…12,14,15 But other in vitro studies and more recent in vivo data questioned the specificity of CD146 expression for CECs. 14,[16][17][18] Yet, CD146 is extensively used to identify circulating cells of endothelial lineage and to distinguish them from leukocytes in preclinical and clinical studies. 3,12,13,19,20 Therefore, the identification of CECs and progenitor cell populations by CD146 must be rigorously validated in the blood of cancer patients.…”

Suction blister fluid as potential body fluid for biomarker proteins

“…Interleukin-6 signal transducer (gp130) S, C M Heart failure related [99,100], HIV infection [101], tumor related [102], scleroderma [51], chronic renal failure [103], fibromyalgia [104], inflammatory disorders of the skin [105] 3/2 [122], insulin resistance in obese males [123], cardiovascular mortality in elderly men [124] 10/4 34 Thioredoxin S, Sk M Oxidative stress in patients with rheumatoid arthritis [53], skin cancer related [54] 5/0…”

Computational Flow Cytometric Analysis to Detect Epidermal Subpopulations In Human Skin

“…CD117, a rete ridge marker, is enriched on a mixture of dormant stem cells, melanoblasts, and melanoma cells without expression at the bulge [7,29]. In healthy adult skin, CD146 is expressed at the epidermal appendage and the external root sheath of HFs [30,31]. CD24 is detected in postmitotic, nonclonogenic suprabasal keratinocytes located in the stratum spinosum of the IFE and the outer and inner root sheath of HFs [32,33].…”