A role for ADAM12 in breast tumor progression and stromal cell apoptosis

• Published in: Cancer research (Chicago, Ill.) Vol. 65; no. 11; pp. 4754 - 4761
• Main Authors: KVEIBORG, Marie, FRÖHLICH, Camilla, ALBRECHTSEN, Reidar, TISCHLER, Verena, DIETRICH, Nikolaj, HOLCK, Peter, KRONQVIST, Pauliina, RANK, Fritz, MERCURIO, Arthur M, WEWER, Ulla M
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-06-2005
• Subjects: 3T3-L1 Cells; ADAM Proteins; ADAM12 Protein; Animals; Antineoplastic agents; Apoptosis - physiology; Biological and medical sciences; Breast - cytology; Breast Neoplasms - pathology; Cell Growth Processes - physiology; CHO Cells; Cricetinae; Disease Progression; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Membrane Proteins - physiology; Metalloendopeptidases - physiology; Mice; Mice, Transgenic; Pharmacology. Drug treatments; Stromal Cells - cytology; Tumors; Mammary gland diseases; Cell death; Breast tumor; Tumor progression; Stromal cell; Stromal tumor; Apoptosis
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.can-05-0262

As in developmental and regenerative processes, cell survival is of fundamental importance in cancer. Thus, a tremendous effort has been devoted to dissecting the molecular mechanisms involved in understanding the resistance of tumor cells to programmed cell death. Recently, the importance of stromal fibroblasts in tumor initiation and progression has been elucidated. Here, we show that stromal cell apoptosis occurs in human breast carcinoma but is only rarely seen in nonmalignant breast lesions. Furthermore, we show that ADAM12, a disintegrin and metalloprotease up-regulated in human breast cancer, accelerates tumor progression in a mouse breast cancer model. ADAM12 does not influence tumor cell proliferation but rather confers both decreased tumor cell apoptosis and increased stromal cell apoptosis. This dual role of ADAM12 in governing cell survival is underscored by the finding that ADAM12 increases the apoptotic sensitivity of nonneoplastic cells in vitro while rendering tumor cells more resistant to apoptosis. Together, these results show that the ability of ADAM12 to influence apoptosis may contribute to tumor progression.