Expression patterns of lymphangiogenic and angiogenic factors in a model of breast ductal carcinoma in situ

Yu, Minghuan; Tang, Zhuo; Alousi, Sarah; Berk, Richard S.; Miller, Fred; Kosir, Mary Ann

doi:10.1016/j.amjsurg.2007.08.007

« Previous Next »The American Journal of Surgery
Volume 194, Issue 5 , Pages 594-599, November 2007

Expression patterns of lymphangiogenic and angiogenic factors in a model of breast ductal carcinoma in situ

Presented at the 31st Annual Surgical Symposium of the Association of VA Surgeons, Little Rock, AR, May 10–12, 2007

Minghuan Yu, Ph.D., M.D.
- Department of Surgery, Wayne State University, 6C-UHC, 4201 St. Antoine, Detroit, MI 48201, USA
Zhuo Tang, M.D.
- Department of Immunology, Wayne State University, 540 E. Canfield, Detroit, MI 48201, USA
Sarah Alousi, B.A.
- Department of Surgery, Wayne State University, 6C-UHC, 4201 St. Antoine, Detroit, MI 48201, USA
Richard S. Berk, Ph.D.
- Department of Immunology, Wayne State University, 540 E. Canfield, Detroit, MI 48201, USA
Fred Miller, Ph.D.
- Breast Program, Karmanos Cancer Institute, 4100 John R, Detroit, MI 48201, USA
Mary Ann Kosir, M.D.
- Department of Surgery, Wayne State University, 6C-UHC, 4201 St. Antoine, Detroit, MI 48201, USA
- Breast Program, Karmanos Cancer Institute, 4100 John R, Detroit, MI 48201, USA
- Surgical Service, John D. Dingell VA Medical Center, 4646 John R, Detroit, MI 48201, USA
- Corresponding author. VAMC (11S)/Wayne State University, 4646 John R, Detroit, MI 48201. Tel.: +1-313-576-3970; fax: +1-313-576-1002.

Received 25 May 2007; received in revised form 12 July 2007

Abstract

Background

Foci of invasion are found in greater than 20% of excised specimens of breast ductal carcinoma in situ (DCIS). Since lymphangiogenesis markers are associated with the potential for increased lymph node metastasis, the purpose of the current study was to determine expression of lymphangiogenesis molecular markers in a model of aggressive DCIS.

Methods

From the MCF10A xenograft model, comedo type MCF10DCIS.com cells, premalignant MCF10AT, and invasive MCF10CA1a.cl1 cells were tested. Invasion was tested by Matrigel invasion assays (Becton-Dickinson, Bedford, MA). Gene expression was determined by reverse transcriptase–polymerase chain reaction and protein expression by immunoblot, normalized to β-actin.

Results

MCF10DCIS.com cells were 4-fold more invasive than MCF10AT cells (P < .01), and expressed several-fold more mRNA and protein than MCF10AT and MCF10CA1a.cl1 cells for vascular endothelial growth factor C, vascular endothelial growth factor D, and lymphatic vessel endothelial hyaluronan receptor 1 (P < .01).

Conclusions

A subset of comedo-type DCIS cells are invasive, and expression of lymphangiogenesis markers is greater at the mRNA and protein levels than by invasive cancer cells (P < .01). These additional molecular markers may characterize aggressive DCIS more precisely.

Keywords: Ductal carcinoma in situ, Lymphangiogenesis, Vascular endothelial growth factor D