mRNA expression of tumor‐associated antigens in melanoma tissues and cell lines

Abstract

Tumor-associated antigens (TAA) are increasingly used as specific targets for immune therapy of malignant melanoma. The aim of the present study was to provide a basis for selecting the most suitable TAA by analyzing the mRNA expression of a large panel of TAA by RT-PCR and Northern blotting. We have chosen primers differentiating four groups of TAA (MAGE-A, MAGE-B, and two groups of GAGE-genes) and 13 individual TAA (MAGE-A2 and -A3, RAGE-1, -2, -3, and -4, LAGE-1a and -1b, NY-ESO-1, GAGE-1, SSX-2, SCP-1, and cTAGE-1) based on most recent sequence data. In addition, the RAGE-gene family has been separated into its four members by a novel designed nested PCR, which was confirmed by Northern analysis. Furthermore, the chromosomal organization and relationship between the RAGE-family and MOK was analyzed. RAGE-4 mRNA could be shown for the first time to be present in testis tissue. The most frequently expressed TAA were the MAGE-A and the GAGE-3,-4,-5,-6,-8 group, whereas among individual TAA MAGE-A2, -A3, RAGE-1, -3, and LAGE-1a/b were found within most specimens and are thus promising candidates for immune therapy. In comparison, melanoma metastatic specimens and cell lines show similar profiles of TAA expression, but individual TAA differ notably between both types of samples indicating that results from cell lines are not always applicable to tumor specimen.

Clinical Implications of High-mobility Group Box-1 (HMGB1) and the Receptor for Advanced Glycation End-products (RAGE) in Cutaneous Malignancy: A Systematic Review

“…The remaining investigations of melanocytic cases were focused on RAGE expression. In one study, the majority of metastatic melanoma tissue analyzed by reverse transcription polymerase chain reaction, were found to positively express RAGE (25). Similarly, another study detected elevated RAGE immunohistochemical reactivity in the cytoplasm of melanoma cells, while normal skin expressed minimal levels (26).…”

“…Full-text review eliminated six studies due to inappropriate data (use of non-human samples, cell culture only, or animal models) or topic irrelevance to the present review. Ultimately, nine articles were included in this review (25,26,21,(27)(28)(29)(30)(31)(32). The majority of the included studies investigated the role of HMGB1 or RAGE in frozen or formalin-fixed paraffin-embedded (FFPE) tissue from patients with melanoma (25,26,28,29,32).…”

Expression of cancer–testis antigens in endometrial carcinomas using a tissue microarray

“…[14][15][16][17][18][19][20] NY-ESO-1 21,22 has been isolated in esophageal carcinoma but has also been found in several other malignancies, such as melanoma; neuroblastoma; carcinoma of the ovary, breast, and lung; and in synovial sarcoma. [23][24][25][26][27][28][29] The CT7 antigen was identified by the SEREX approach using a melanoma cell line SK-MEL37 and allogeneic sera from a melanoma patient. 30 CT7 is identical to MAGE-C1, identified independently by another group using representational difference analysis.…”

Restriction of GAGE protein expression to subpopulations of cancer cells is independent of genotype and may limit the use of GAGE proteins as targets for cancer immunotherapy

“…Interestingly, expression of several CT antigens, including GAGE, can be induced by the hypomethylating agent 5-aza-2 0 -deoxycytidine (Sigalotti et al, 2002), and it has been shown that induction of transcription correlates with hypomethylation of CT antigen promoters (Janssen et al, 1999;De Smet et al, 2004). There also seem to be individual differences in the regulation of the transcription of GAGE genes since the GAGE members are not always co-expressed (Kobayashi et al, 2000;Eichmuller et al, 2002;Eichmuller et al, 2003).…”

“…GAGE gene transcripts have been found in numerous types of cancers, most frequently in melanomas (De Backer et al, 1999;Eichmuller et al, 2002) and lung adenocarcinomas (De Backer et al, 1999), in which up to 54% of specimens were found to express GAGE, as well as in gastric cancers (Zambon et al, 2001;Kong et al, 2004) and hepatocellular carcinomas (Kobayashi et al, 2000).…”