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

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An Erratum to this article was published on 27 November 2009

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).

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Abbreviations

FAP:

Familial adenomatous polyposis

APC:

Adenomatous polyposis coli

EGFR:

Epidermal growth factor receptor

rhEGF:

Recombinant human epidermal growth factor

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Acknowledgments

This study was supported by research grants from the Desmoid Tumor Research Foundation (DTRF) and the Huntsman Cancer Foundation. The authors thank Diane M. Miller for assistance with the figures and acknowledge the support provided by the Microarray Core Facility, Huntsman Cancer Institute, and the NCI Cancer Center support grant P30CA042014.

Author information

Authors and Affiliations

  1. SARC™ Laboratory, Sarcoma Services, Department of Orthopaedics and Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA

    David E. Joyner, Sylvia H. Trang & R. Lor Randall

  2. Sinai Hospital Cancer Institute, Baltimore, MD, 21215-5271, USA

    Albert J. Aboulafia

  3. Department of Orthopaedics, SUNY Upstate Medical University, Syracuse, NY, 13202, USA

    Timothy A. Damron

Authors
  1. David E. Joyner
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  2. Sylvia H. Trang
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  3. Albert J. Aboulafia
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  5. R. Lor Randall
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Correspondence to David E. Joyner.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s10689-009-9304-2

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Joyner, D.E., Trang, S.H., Aboulafia, A.J. et al. FAP-associated desmoid invasiveness correlates with in vitro resistance to doxorubicin. Familial Cancer 8, 569–580 (2009). https://doi.org/10.1007/s10689-009-9288-y

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