Advanced therapies in cancer – Tumor cells biology

Objective:
The purpose of OncoGen Center is to target the tumor development on the aspects of tumor cells, tumor microenvironment, tumor immunological response, finally resulting in personalized anti-cancer therapy. The key obstacle for a breakthrough in cancer therapeutics is that tumors are thought to result from the unregulated growth of a single cell type that has accumulated random gene mutations, whereas the true mark of malignancy is the ability of cancerous cells to break down tissue architecture, invade through the disrupted tissue boundaries and metastasize to distant organ sites.

a) Tumor-associated fibroblasts as novel target in anti-tumor therapy – identification of origin, role and characteristic molecular markers (PNII-Idei, 318/2011, 2012-2016)

Short description:
Microenvironment has a key role in tumor development, so that identification of stromal targets for cancer therapeutics is of great interest and could provide strategies that will complement therapies directed against cancer cells. The failure of immune surveillance to prevent tumor development and the observation that effective therapies can become ineffective over time suggest that mechanisms exist, whereby tumors can escape the immune system. Tumor associated fibroblasts (TAFs), potentially originating from recruitment of resident tissue stem cells, bone marrow-derived mesenchymal stem cells (MSCs) or epithelial to mesenchymal transition within tumors, are important for tumor progression, providing both functional and structural supportive environment. The true origin, role, and biological characteristics of TAFs are not fully understood yet.

The main objective of this project is to fully characterize TAFs obtained from solid tumors (breast cancer), to establish their origin and role within the tumor stroma. MSCs are used as normal/precursor cells to which the TAFs will be compared in order to identify specific marker, which would be used as target in prospective anti-tumor therapy designs. Cellular therapies in vitro prototype proposed by this project involves enhancement of human cytotoxic T lymphocytes (CTL) functionally active against TAF-derived specific antigen.

Link: www.taf-research.ro

Relevant publications:

  1. Paunescu V, Bojin FM, Gavriliuc OI, Taculescu EA, Ianos R, Ordodi VL, Iman VF, Tatu CA. Enucleation: a possible mechanism of cancer cell death. J Cell Mol Med. 2014; 18(6): 962-5.
  2. Tatu RF, Anusca D, Groza S, Marusciac L, Bojin F, Tatu CS, Hurmuz M, Paunescu V. Morphological and functional characterization of femoral head drilling-derived mesenchymal stem cells. Rom J Morphol Embryol, 2014; 55(4): 3-6.
  3. Bojin FM, Gavriliuc OI, Cristea MI, Tanasie G, Tatu CS, Panaitescu C, Paunescu V. Telocytes within human skeletal muscle stem cell niche. J Cell Mol Med. 2011; 15(10):2269-2272.
  4. Paunescu V, Bojin FM, Tatu CA, Gavriliuc OI, Rosca A, Gruia AT, Tanasie G, Bunu C, Crisnic D, Gherghiceanu M, Tatu FR, Tatu CS, Vermesan S. Tumour-associated fibroblasts and mesenchymal stem cells: more similarities than differences. J Cell Mol Med., 2011; 15(3):635-646.

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