Fresh Tissue Collection and Distribution
Andreas Friedl, MD – Tumor Microenvironment Program
Dr. Friedl and colleagues have studied the importance of stroma in breast cancer development and progression (Figure 1). In research supported by R01 CA107012 (PI Fried), they observed that the cell surface proteoglycan syndecan 1 (Sdc1) is induced in breast carcinoma stromal fibroblast which recapitulates the stromal expression seen during mammary morphogenesis.
Su G, Blaine SA, Qiao D, Friedl A. Membrane type 1 matrix metalloproteinase-mediated stromal syndecan-1 shedding stimulates breast carcinoma cell proliferation. Cancer Res. 2008;68(22):9558-65. PMCID: PMC2877371.
Figure 1. Carcinoma associated fibroblasts (CAF) stimulate T47D cell proliferation significantly more than normal fibroblasts (NF), and inhibition of MT1-MMP reverses the growth advantage. (A) Immunofluorescent staining of CAF and NF grown on chamber slides to 80 % confluency, fixed and stained with anti-S100A4/FSP1 (FSP) and anti-alpha smooth muscle actin (SMA) antibodies. (B) Differences in T47D proliferation in CAF and NF. The co-cultures were treated with anti-MT1-MMP or rabbit IgG for three days and co-culture-stimulated T47D cell growth was calculated as mucin-1 positive area of T47D and CAF or NF co-culture minus mucin-1 positive area of T47D monoculture.
Tissue Microarray Creation and AQUA
Paul C. Marker, PhD – Cancer Genetics Program
Drs. Marker, Collier, Huang and colleagues conducted a mouse genetic screen using the Sleeping Beauty transposon system to identify candidate prostate cancer (PrCa) genes in mice. In research supported by multiple grants (PI Marker: W81XWH-05-1-053, R01 AG024278; PI Collier K01 CA122183), they identified candidate PrCa genes at common insertion sites including Pde4d (Figure 2).
Rahrmann EP, Collier LS, Knutson TP, Doyal ME, Kuslak SL, Green LE, Malinowski RL, Roethe L, Akagi K, Waknitz M, Huang W, Largaespada DA, Marker PC. Identification of PDE4D as a proliferation promoting factor in prostate cancer using a Sleeping Beauty transposon-based somatic mutagenesis screen. Cancer Res. 2009;69(10):4388-97. PMCID: PMC2710962.
Figure 2. PDE4D is over-expressed in human prostate cancer patient samples. (A) Fluorescent images from a human PrCa TMA. The TMA was stained with anti-E-cadherin/anti-cytokeratin cocktail to identify the epithelial cell cytoplasm, DAPI to identify nuclei and anti-PDE4D for PrCa that was co-localized with the epithelial-specific stain (yellow signal in top right). A parallel TMA was stained in the presence of a PDE4D peptide (lower row) which was blocked indicating that the anti-PDE4D signal reflected specific staining for PDE4D. (B) Graph showing AQUA results for PDE4D staining on the TMA. The higher expression in patients with PrCa relative to patients with benign prostatic hyperplasia (BPH) was statistically significant (P<0.001 by T-test).