Expression patterns of lymphangiogenic and angiogenic factors in a model of breast ductal carcinoma in situ.
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 beta-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.
Yu
Minghuan
M
Department of Surgery, Wayne State University, 6C-UHC, 4201 St. Antoine, Detroit, MI 48201, USA.
Tang
Zhuo
Z
Alousi
Sarah
S
Berk
Richard S
RS
Miller
Fred
F
Kosir
Mary Ann
MA
D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression; D006801:Humans; D042583:Lymphangiogenesis / Q000502:physiology; D008207:Lymphatic Metastasis; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis; D042643:Vascular Endothelial Growth Factor D / Q000096:biosynthesis; D033921:Vesicular Transport Proteins / Q000096:biosynthesis
D043925:Angiogenesis Inducing Agents; C119248:LYVE1 protein, human; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D033921:Vesicular Transport Proteins