Abstract

CD109, a glycosylphosphatidylinositol-anchored glycoprotein, is expressed at high levels in some human tumors including squamous cell carcinomas. As CD109 is reportedly cleaved by furin and its soluble form is secreted into culture medium in vitro, we hypothesized that CD109 could serve as a tumor marker in vivo. In this study, we investigated CD109 as a novel serum tumor marker using transgenic mice that overexpress mouse CD109 (mCD109-TG mice) and tumor xenografted mice inoculated with human CD109 (hCD109)-overexpressing HEK293 cells. In sera and urine of mCD109-TG mice, mCD109 was detected using western blotting. In xenografted mice, hCD109 secreted from inoculated tumors was detected in sera, using western blotting and CD109 ELISA. Concentrations of tumor-secreted CD109 increased proportionally as tumors enlarged. Concentrations of secreted CD109 decreased notably by 17 h after tumor resection, and became undetectable 48 h after resection. The half-life of tumor-secreted CD109 was about 5.86±0.17 h. These results indicate that CD109 is present in serum as a soluble form, and suggest its potential as a novel tumor marker in patients with cancers that express CD109.

Highlights

  • CD109, a glycosylphosphatidylinositol (GPI)-anchored cellsurface glycoprotein, is a member of the a2-macroglobulin/ C3,C4,C5 family [1,2,3,4]

  • We investigated the availability of CD109 as a tumor marker, using Mouse CD109 (mCD109)-TG mice and HEK293 xenografted mice

  • CD109 is highly expressed in some tumors, especially in squamous cell carcinomas (SCCs) of lung, esophagus, uterus and oral cavity, whereas it is expressed by very limited cells in normal tissues such as myoepithelial cells of the mammary, salivary and lacrimal glands, and basal cells of the prostate and bronchial epithelia

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Summary

Introduction

CD109, a glycosylphosphatidylinositol (GPI)-anchored cellsurface glycoprotein, is a member of the a2-macroglobulin/ C3,C4,C5 family [1,2,3,4]. Whereas CD109 is expressed in only limited cell types in normal human and mouse tissues, including myoepithelial cells of the breast, salivary, lacrimal, and bronchial secretary glands; basal cells of the prostate and bronchial epithelia; and basal to suprabasal layers of epidermis [8,9,10,11,12,13], its expression is frequently detected in several tumor tissues, including squamous cell carcinomas (SCCs) of the oral cavity, esophagus, lung and uterus, basal-like breast carcinoma, malignant melanoma of the skin, and urothelial carcinoma of the bladder, using immunohistochemical studies with anti-CD109 antibody [8,9,10,11,12], [14,15,16]. High expression of CD109 is frequently detected in premalignant squamous epithelial lesions, and was associated with differentiation of SCCs in the oral cavity [14]. CD109 has been shown to be cleaved by furin into two forms, a 180-kDa soluble form and a 25-

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