In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 2302-2302
Abstract:
Lung cancer is the leading cause of cancer deaths, and non-small-cell lung cancer (NSCLC) is the most prevalent form of lung cancer. The tumor suppressor gene CADM1/TSLC1 was originally identified in NSCLC. CADM1 encodes an immunoglobulin superfamily cell adhesion molecule. CADM1 is inactivated by deletion and/or promoter methylation of the gene in 40-60% of NSCLC, especially in their advanced stages. Previously we generated conventional Cadm1-deficient mice and found that around 40% of Cadm1-deficient mice spontaneously developed lung adenoma and adenocarcinoma by 15 months of age. To assess the precise role of CADM1 in suppression of lung tumorigenesis, we crossed Cadm1-deficient mice to conditional K-ras-mutant mice, well-established mouse models of lung cancer. The K-ras-mutant mice are shown to develop multiple lung adenocarcinomas by 25 weeks after administration of adenovirus expressing Cre recombinase followed by the activation of oncogenic K-ras. We then analyzed the development of lung tumors in K-ras-mutant (K) mice and K-ras-mutant Cadm1-deficient (KC) mice. Loss of Cadm1 results in enlargement of the size of alveolar tumors (adenomas or adenocarcinomas) as well as higher tumor grades. The most malignant histology of vascular or pleural invasion was only detected in tumors from KC mice. On the other hand, the size of the bronchial tumors was larger in K mice than in KC mice. Immunohistochemical analysis of bronchial marker SOX2 showed that adenomas or adenocarcinomas expressing SOX2 were larger in KC mice, indicating that loss of Cadm1 enhanced the rapid growth of alveolar tumors and thereby impaired the growth of bronchial tumors originated from the common stem cells, bronchio-alveolar stem cells (BASCs). Furthermore, tumors from K mice showed frequent loss of CADM1 expression and the tumors with low expression of CADM1 exhibited more malignant histological features. These results suggest that loss of Cadm1 promotes the malignant progression of alveolar tumor. Citation Format: Takeshi Ito, Masayoshi Nagata, Taketo Kawai, Mika Sakurai-Yageta, Akihiko Ito, Akiteru Goto, Daisuke Matsubara, Yoshinori Murakami. Analysis of the role of CADM1 in suppression of lung cancer using Cadm1-deficient mice. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2302. doi:10.1158/1538-7445.AM2015-2302
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2015-2302
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2015
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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