Hedgehog signaling pathway is a possible therapeutic target for gastric cancer

Kosuke Yanai, Shuntaro Nagai, Junji Wada, Naoki Yamanaka, Masafumi Nakamura, Nobuhiro Torata, Hirokazu Noshiro, Masazumi Tsuneyoshi, Masao Tanaka, Mitsuo Katano

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)55-62
Number of pages8
JournalJournal of Surgical Oncology
Volume95
Issue number1
DOIs
Publication statusPublished - Jan 1 2007

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

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