Hedgehog signaling pathway is a possible therapeutic target for gastric cancer

• Published in: Journal of surgical oncology 2007-01, Vol.95 (1), p.55-62
• Main Authors: Yanai, Kosuke, Nagai, Shuntaro, Wada, Junji, Yamanaka, Naoki, Nakamura, Masafumi, Torata, Nobuhiro, Noshiro, Hirokazu, Tsuneyoshi, Masazumi, Tanaka, Masao, Katano, Mitsuo
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adenocarcinoma - secondary; Adult; Aged; Aged, 80 and over; Carcinoma, Signet Ring Cell - metabolism; Carcinoma, Signet Ring Cell - pathology; Carcinoma, Signet Ring Cell - secondary; Cell Line, Tumor; Female; gastric cancer; Gli1; Hedgehog Proteins - physiology; hedgehog signaling; histologic heterogeneity; Humans; lymph node metastasis; Lymph Nodes - metabolism; Lymph Nodes - pathology; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Oncogene Proteins - analysis; Oncogene Proteins - genetics; Receptors, Cell Surface - metabolism; Signal Transduction - physiology; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Trans-Activators - analysis; Trans-Activators - genetics; Trans-Activators - physiology; Transcription Factors - metabolism; Zinc Finger Protein GLI1
• ISSN: 0022-4790; 1096-9098
• DOI: 10.1002/jso.20606

Background and Objectives It has been shown that the hedgehog (Hh) signaling pathway is activated in gastric cancer. To investigate the viability of the Hh pathway as a therapeutic target, we analyzed activation of the Hh pathway in gastric cancer. Methods Surgically resected gastric carcinoma specimens and lymph nodes were analyzed immunohistochemically. We used the percentage of cancer cells with nuclear translocation of Gli1 as a marker of Hh pathway activation. Results Nuclear localization of Gli1 was higher in 28 undifferentiated‐type tumors than in 30 differentiated‐type tumors. Eighteen of the fifty‐eight cancer specimens consisted of a mixture of a histologically predominant part and a small area with different histology. In these 18 tumors, the percentage of cells showing nuclear staining of Gli1 was higher in the undifferentiated‐type part than in the differentiated‐type part. Nuclear staining of Gli1 in primary tumors was positively correlated with lymph node metastasis. The Gli1 nuclear staining percentage of metastatic lymph nodes correlated closely with that of each primary carcinoma. Cyclopamine, a Hh pathway inhibitor, suppressed the growth of gastric cancer cells in vitro. Conclusions The Hh pathway may be a useful therapeutic target for such as undifferentiated‐type gastric cancer with lymph node metastasis. J. Surg. Oncol. 2007;95:55–62. © 2006 Wiley‐Liss, Inc.