FAP-associated desmoid invasiveness correlates with in vitro resistance to doxorubicin.
Desmoid tumors are locally invasive myofibroblastic 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 significantly 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 antigen 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).
Joyner
David E
DE
Department of Orthopaedics, Sarcoma Services, SARC Laboratory, and Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, USA. david.joyner@hci.utah.edu
Trang
Sylvia H
SH
Aboulafia
Albert J
AJ
Damron
Timothy A
TA
Randall
R L
RL
Randall
R Lor
RL
D011125:Adenomatous Polyposis Coli / Q000150:complications / Q000235:genetics / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018222:Desmoid Tumors / Q000235:genetics / Q000473:pathology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; D004317:Doxorubicin; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1