Scientific Session I: Cell fusion

1. Scientific Session I: Cell fusion • The amoeboid phenotype in cancer (Michael Freeman – Children’s Hospital) • Blebbing, DRF3 (inh. mets by inh the mesenchymal to amoeboid transition) • A role for endogenous cell fusion in cancer progression (Melissa Wong - OHSU) • Fusion of BMDCs with intestinal epithelial cells increased in an inflammatory microenvironment Inflammation and proliferation act together to mediate intestinal cell fusion. Davies PS, PLoS One. 2009 Aug 6;4(8) • Myeloma induced-cell fusion: implication for bone disease and immunobiology (MadhavDhodapkar – Yale)

2. Scientific Session II: Tumor Immunology • Targeting pro-tumor immunity (Lisa Coussens – UCSF) FcR gamma Activation Regulates Inflammation-Associated Squamous Carcinogenesis. Andreu P et al., Cancer Cell. 2010 Feb 3. CD45+ leukocytes in human solid tumors: which subpopultaion promotes tumor progression and mets formation? Lineage specific markers Profile of immune infiltrate in neoplasic skin (K14, HPV16):  Role of FcR gamma expr by macrophages  Role for B- cells (depletion: slows carcinoma progression)

3. Scientific Session II: Tumor Immunology • Antigen cross presented on tumor stroma: An essential target for eradication of cancer (Hans Schreiber – U. Chicago) • From infection to obesity: control of tumor progression and metastasis by pro-inflammatory signals (Michael Karin – UCSD) • 2 different types of inflammation: (model prostate cancer) • Tumor-associated, • Therapy-induced acute necrosis, inflammation Androgen dpdt Cancer  Necrosis  Androgen indpdt K (IKKa, Stat3): castration-resistant phenotype. cytokine castration

4. Scientific Session III: Tumor Dormancy • Dissemination of prostate cancer cell to bone marrow (Robert Vessella – U. Washington) CTC vs DTC Question: Can we identify which DTCs will eventually form mets – What breaks dormancy? Prostate cancer: 67% of DTC in the bm  isolation and characterization of gene expression

5. Scientific Session III: Tumor Dormancy • Mechanisms driving dormancy of DTC: th eprelude to metastasis (Julio Aguirre-Ghiso – NYU) Hep3: squamous carcinoma cells (D- and T-) p21 and p38: cell cycle inhibitor, active in dormant lesions Col1a1, ADAM10; MMP1 are increased in dormant lesions ER stress: ATF6 transcription factor, active in dormant lesions (nuc. localization), control the survival of dormant tumor cells (mTOR, Rheb) Only 8 genes differentially expressed betw T- and D-Hep3

6. Scientific Session IV: Tumor Microenvironment: Translational aspects • Diverse role of mesenchymal lineages in cancer progression and metastasis (Raghu Kalluri – BIDMC) • Caveolin -1 in the tumor stromal microenvironment: translational implication for prognosis and treatment stratification in breast cancer (Michael Lisanti) • Targeting the tumor stroma with protease-activated “smart bombs” (Samuel Denmeade – Johns Hopkins) Carrier peptide ---- (Pro)Drug (thapsigargin)  Can stromal cells be selectively killed by expression of unique protease (FAP: expr by K fbb in 90% of epithelial cancers)? Anti-tumor effect?

7. Scientific Session IV: Tumor Microenvironment: Translational aspects • Breast tumor microenvironment: predictor of clinical outcome and contributes to tumor heterogeneity (Morag Park – McGill) Question: Could gene expression profile derived from the microenvironment predict the clinical outcome? • Identification of 6 different subtypes of breast cancer-associated stroma: • µenv characterized by matrix remodeling (MMPs, TGFb…) // ER/PR/Her2 - // bad prognosis // basal-like carcinoma • Hypoxic µenv (Osteopontin, Il8) // ER+/-/Her2+ • Angiogenic µenv (LOXL2, osteopontin) // ER+/PR+/- • 3 gp of patients with different outcome (poor, intermediate, good): the gene cluster associated with a good outcome correspond to an inflammatory µenv. Question: Can we predict recurrence in tumor stroma? • Poor outcome: elevated osteopontin • Intermediate outcome: OGN