FAP-associated desmoid invasiveness correlates with in vitro resistance to doxorubicin David E. Joyner Æ Sylvia H. Trang Æ Albert J. Aboulafia Æ Timothy A. Damron Æ R. Lor Randall Published online: 2 September 2009 Ó Springer Science+Business Media B.V. 2009 Abstract Desmoid tumors are locally invasive myofib- roblastic lesions that arise predominantly in the abdominal wall or shoulder girdle and are prone to aggressive local recurrences without metastases. We hypothesized the intrinsic invasiveness and drug resistance displayed by cells derived from a familial adenomatous polyposis (FAP)-associated desmoid tumor would surpass the response shown by cells derived from sporadic desmoid tumors. In vitro cell motility and expression of motility- associated genes were quantified using Boyden Chambers and Enzyme-Linked ImmunoSorbent Assays, respectively. Doxorubicin resistance was quantified by Trypan Blue dye exclusion. cDNA microarrays identified genes responsive to doxorubicin. FAP-associated tumor cells were signifi- cantly more invasive and refractory to doxorubicin than were cells extracted from sporadic tumors. Pro-MMP1 protein predominated over MMP3 in FAP-associated cell culture supernatants, while MMP3 was the dominant anti- gen in sporadic tumor cell supernatants. Three genes associated with apoptosis were identified by microarray, two prosurvival genes overexpressed in FAP-associated cell cultures (NTN1, TNFRSF10C) and one proapoptosis gene overexpressed in sporadic tumor cell cultures (FOXL2). Keywords Apoptosis-related genes Á Desmoid Á Drug resistance Á FAP Á In vitro Á Microarray Á Motility Abbreviations FAP Familial adenomatous polyposis APC Adenomatous polyposis coli EGFR Epidermal growth factor receptor rhEGF Recombinant human epidermal growth factor Introduction Desmoid tumors, also known as aggressive fibromatosis, are rare, benign myofibroblastic lesions that are prone to aggressive local recurrences without metastases [15, 23]. Although the etiology is uncertain, desmoids have been associated with trauma, hormonal activity, and genetic alterations. They often develop in women during or after pregnancy and are probably of monoclonal origin [1, 6, 8, 30, 33]. Sporadic desmoids have a predilection for arising in the proximal extremities or abdominal wall, while intra- abdominal desmoids tend to be associated with familial neoplastic syndromes such as familial adenomatous pol- yposis (FAP) [15, 21, 37]. A majority (C50%) of FAP- associated tumors are intra-abdominal rather than extra- abdominal, with C85% mesenteric [21]. FAP-associated desmoids reportedly result from germline mutations to the adenomatous polyposis coli (APC) gene followed by somatic inactivation of the wild-type APC allele. Sporadic desmoids may also contain mutations in the APC gene, but D. E. Joyner (&) Á S. H. Trang Á R. L. Randall SARC TM Laboratory, Sarcoma Services, Department of Orthopaedics and Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, USA e-mail: david.joyner@hci.utah.edu A. J. Aboulafia Sinai Hospital Cancer Institute, Baltimore, MD 21215-5271, USA T. A. Damron Department of Orthopaedics, SUNY Upstate Medical University, Syracuse, NY 13202, USA 123 Familial Cancer (2009) 8:569–580 DOI 10.1007/s10689-009-9288-y