Hedgehog signaling pathway is a possible therapeutic target for gastric cancer.
OBJECTIVE
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.
Yanai
Kosuke
K
Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Nagai
Shuntaro
S
Wada
Junji
J
Yamanaka
Naoki
N
Nakamura
Masafumi
M
Torata
Nobuhiro
N
Noshiro
Hirokazu
H
Tsuneyoshi
Masazumi
M
Tanaka
Masao
M
Katano
Mitsuo
M
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018279:Carcinoma, Signet Ring Cell / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D045744:Cell Line, Tumor; D005260:Female; D053823:Hedgehog Proteins / Q000502:physiology*; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D015513:Oncogene Proteins / Q000032:analysis / Q000235:genetics; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1
D053823:Hedgehog Proteins; D015513:Oncogene Proteins; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1