Maspin and Suppression of Tumor Metastasis
Maspin is a member of the family of Serine Protease Inhibitors or serpins. Since its discovery in 1994, considerable amount of information has been gathered regarding its role in normal tissue development and pathological processes, such as tumorigenesis and metastasis. It is now well recognized that maspin is unique serpin with tumor suppressing activities. Like many of its serpin family members, maspin possesses multiple functions, including antimigration, anti-invasion, induction of apoptosis, and anti-angiogenesis. Its functions are dependent on its cellular locations: extracellular, intracellular, mitochondria, and nucleus. This chapter covers three major topics on maspin research: biological functions of maspin, regulation of maspin gene expression, and modeling breast cancers in mice with maspin as a paradigm. Our goal is to provide readers with a comprehensive analysis of maspin study by many maspin researchers in the past few years and also with unique insights on our study of maspin functions in mouse model in vivo.
KeywordsMammary Tumor Mammary Epithelial Cell Maspin Expression Normal Mammary Epithelial Cell Sensitize Breast Cancer Cell
- Khalkhali-Ellis Z, Christian AL, Kirschmann DA, Edwards EM, Rezaie-Thompson M, Vasef MA, Gruman LM, Seftor RE, Norwood LE, Hendrix MJ (2004) Regulating the tumor suppressor gene maspin in breast cancer cells: a potential mechanism for the anticancer properties of tamoxifen. Clin Cancer Res 10:449–454PubMedCrossRefGoogle Scholar
- Law RH, Irving JA, Buckle AM, Ruzyla K, Buzza M, Bashtannyk-Puhalovich TA, Beddoe TC, Nguyen K, Margaret Worrall D, Bottomley SP et al (2005) The high resolution crystal structure of the human tumour suppressor maspin reveals a novel conformational switch in the G-helix. J Biol Chem 280(23):22356–22364PubMedCrossRefGoogle Scholar
- Li M, Hu J, Heermeier K, Hennighausen L, Furth PA (1996) Expression of a viral oncoprotein during mammary gland development alters cell fate and function: induction of p53-independent apoptosis is followed by impaired milk protein production in surviving cells. Cell Growth Differ 7:3–11PubMedGoogle Scholar
- Pemberton PA, Wong DT, Gibson HL, Kiefer MC, Fitzpatrick PA, Sager R, Barr PJ (1995) The tumor suppressor maspin does not undergo the stressed to relaxed transition or inhibit trypsin-like serine proteases. Evidence that maspin is not a protease inhibitory serpin. J Biol Chem 270:15832–15837PubMedCrossRefGoogle Scholar
- Yin S, Lockett J, Meng Y, Biliran H Jr, Blouse GE, Li X, Reddy N, Zhao Z, Lin X, Anagli J et al (2006) Maspin retards cell detachment via a novel interaction with the urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor system. Cancer Res 66:4173–4181PubMedCrossRefGoogle Scholar