FAP-associated desmoid invasiveness correlates with in vitro resistance to doxorubicin

David E. Joyner, Sylvia H. Trang, Albert J. Aboulafia, Timothy A. Damron, R Randall

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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).

Original languageEnglish (US)
Pages (from-to)569-580
Number of pages12
JournalFamilial Cancer
Volume8
Issue number4
DOIs
StatePublished - Dec 1 2009
Externally publishedYes

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Aggressive Fibromatosis
Adenomatous Polyposis Coli
Doxorubicin
Neoplasms
Cell Culture Techniques
Genes
Trypan Blue
Abdominal Wall
In Vitro Techniques
Oligonucleotide Array Sequence Analysis
Drug Resistance
Cell Movement
Coloring Agents
Enzyme-Linked Immunosorbent Assay
Apoptosis
Neoplasm Metastasis
Antigens
Recurrence

Keywords

  • Apoptosis-related genes
  • Desmoid
  • Drug resistance
  • FAP
  • In vitro
  • Microarray
  • Motility

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Genetics(clinical)
  • Cancer Research

Cite this

FAP-associated desmoid invasiveness correlates with in vitro resistance to doxorubicin. / Joyner, David E.; Trang, Sylvia H.; Aboulafia, Albert J.; Damron, Timothy A.; Randall, R.

In: Familial Cancer, Vol. 8, No. 4, 01.12.2009, p. 569-580.

Research output: Contribution to journalArticle

Joyner, David E. ; Trang, Sylvia H. ; Aboulafia, Albert J. ; Damron, Timothy A. ; Randall, R. / FAP-associated desmoid invasiveness correlates with in vitro resistance to doxorubicin. In: Familial Cancer. 2009 ; Vol. 8, No. 4. pp. 569-580.
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