Identification of the Decay-Accelerating Factor CD55 as a Peanut Agglutinin–Binding Protein and Its Alteration in Non–Small Cell Lung Cancers

Abstract

Purpose: Peanut agglutinin (PNA) recognizes tumor-associated carbohydrates. In this study, we aimed to identify the core protein harboring PNA-binding sugars in the human lung and to explore the relationship with the pathology of primary non^small cell lung cancers (NSCLC). Experimental Design: PNA lectin blotting was used to detect PNA-binding proteins in the microsomal fraction of lung tissue from 24 patients with NSCLC. The 55-to 65-kDa core peptide PNA-binding protein was characterized by enzymatic treatment and identified by immunoprecipitation and affinity chromatography. The expression level and increase in size of the 55-to 65-kDa PNA-binding protein/decay-accelerating factor (DAF) were compared between normal and tumor regions of the tumor tissue by Western blotting and quantitative PCR. Results: The 55-to 65-kDa PNA-binding protein was observed in human lung. This was a glycosylphosphatidylinositol-anchored membrane protein carrying O-linked carbohydrates. This core protein was identified as DAF, one of the complementary regulatory proteins. DAF was enlarged to 65 to 75 kDa in NSCLC tumor lesions due to sialylation in the sugar moiety. At the transcription level, DAF levels were significantly lower in tumor regions, suggesting its down-regulation in NSCLC cells. Conclusions: DAF was identified as a new PNA-binding protein in the human lung. The downregulation and heavy sialylation of DAF was associated with pathology in NSCLC, and these alterations make this protein a potential marker for NSCLC.Carbohydrates on the cell surface play an important role in several metastatic processes by influencing cell-cell and cellextracellular matrix protein interactions (1). Peanut agglutinin (PNA) is a plant lectin isolated from Arachis hypogaea that preferentially recognizes galactose h1-3N-acetylgalactosamine linkage in O-linked glycans (2, 3), also called tumor-associated antigen (T-antigen) or Thomsen-Friedenreich antigen (4). The expression levels and localization patterns of PNA-recognizing carbohydrates have been reported to correlate with the aggressiveness of several cancers, including colorectal cancer, breast cancer, and malignant melanoma (1,3,5,6). In lung cancers, however, there are few reports about the relationship between T-antigen expression and clinicopathologic variables (7). We previously reported that the expression of PNArecognizing carbohydrates was significantly correlated to lymphatic vessel invasion and a high lymph node metastatic rate in lung adenocarcinoma tissue (8). However, the precise mechanism of involvement of PNA-binding sugars in metastasis is unclear and there is no information on the core protein harboring PNA-binding sugars in lung cancers. To date, several PNA-binding proteins or PNA receptors have been identified, including CD8, CD43, CD44, CD45, gp200, polymorphic epithelial mucin, and .In the present study, we identified decay-accelerating factor (DAF; CD55) as a new core protein harboring PNA-binding sugars in the lung. DAF is present on all blood elements and m...

A common CD55 rs2564978 variant is associated with the susceptibility of non-small cell lung cancer

“…CD55 also inhibits C3 and C5 activation and thereby limits complement-dependent cell cytotoxicity (CDC) [10, 13]. Studies have demonstrated a down-regulation of CD55 in NSCLC cells [17]. Our present results supported that the CD55 rs2564978 CC genotype was linked to an increased risk of NSCLC.…”

“…The expression CD55 in gastric cancer, colon and breast cancer was significantly greater than in those non-cancer tissues [12–16]. However, studies also demonstrated a down-regulated expression of CD55 in ovarian cancer and lung cancer tissues [17, 18]. In Higuchi's study, CD55 was recognized as a novel PNA-binding protein in the human lung and the down-regulation of CD55 was associated with pathology of primary NSCLC [17].…”

Therapeutic Lessons to be Learned From the Role of Complement Regulators as Double-Edged Sword in Health and Disease

“…There might be a differential effect of CD55 between healthy and cancer cells at play here, as CD55 in NSCLC is not only down-regulated, but also sialylated. Possibly, sialylated CD55 can execute its function longer than regular CD55, as it has a high resistance against proteolysis and can thus be retained on the cell surface for a longer time ( 153 ). Another explanation could be that NSCLC tissue does not require complement regulation as much, as the bulky tissue formation ensures that not all cells are exposed to the alveolar cavity, and thus to complement activity ( 153 ).…”