Research topics

The field of research of this Laboratory is mainly focused on the study of the molecular and cellular basis of tumor growth and progression. The main aim of this research is the identification of novel biological markers, and therefore, molecular targets for the development of innovative therapeutic strategies. Specifically, this Laboratory investigates the mechanisms underlying the activity of both synthetic and natural anticancer compounds in aggressive tumors (advanced prostate cancer, cutaneous melanoma).

In this context, the main aims of this research are:
1) Study of canonical and non-canonical cell death pathways (apoptosis, paraptosis, necroptosis) induced by antitumor compounds and of the molecular mechanisms involved in these processes (endoplasmic reticulum stress, autophagy, mitochondrial dysfunction)
2) Analysis of the metabolic reprogramming in tumor cells as a target of antitumor compounds
3) Isolation and characterization of cancer stem cells
4) Study of the mechanisms of the cross-talk between cancer cells and their microenvironment (immune cells, vascular endothelial cells, adipocytes)
5) Investigation of the role of tumor-derived exosomes in tumor progression and in the cross-talk with the microenvironment
6) Analysis of the mechanisms involved in chemoresistance
7) Characterization of hormone receptors, both membrane and nuclear, and of their transduction pathways in tumor growth and development

Technologies

- 2D and 3D cancer cell cultures
- Isolation and characterization of cancer stem cells (flow cytometry, sphere formation)
- Adipocyte-cancer cell co-cultures (fibroblast differentiation into adipocytes, Oil Red O staining, expression of specific markers)
- Isolation and characterization of human leukocytes (density gradient centrifugation on human blood, Wright-Giemsa staining, analysis of their pro/antitumor phenotype)
- Isolation and characterization of tumor-derived exosomes (ultracentrifugation, flow cytometry)
- Analysis of cell viability (MTT assay, clonogenic assay)
- Analysis of motility/invasivity (Boyden's chamber, adhesion and invasion tests, scratch test)
- Neoangiogenesis analysis (proliferation, migration, motility and tube formation of endothelial cells)
- Analysis of mitochondrial function and oxidative stress (flow cytometry, colorimetric assays)
- Protein analysis (Western blot, Elisa, immunostaining)
- RNA expression analysis (real time RT-PCR), gene overexpression (transfection) and gene silencing (RNA interference)
- DNA recombinant techniques

Collaborators

-Prof. Nico Mitro, University of Milano, Milano
-Dr. Patrizia Procacci, University of Milano, Milano
-Prof. Nicoletta Gagliano, University of Milano, Milano
-Dr. Nadia Zaffaroni, IRCCS-National Institute of Cancer, Milano
-Prof. Giangiacomo Beretta, University of Milano, Milano
-Dr. Maria Rosa Bani, IRCCS-Mario negri Institute of Pharmacoligical Research, Milano
-Dr. Valeria Sibilia, University of Milano, Milano
-Dr. Lavinia Casati, U University of Milano, Milano, Milano
-Dr. Claudio Festuccia, University of L'Aquila, L'Aquila
-Dr.Marilena Manea, University of Konstanz, Germany
-Dr. Edwin Manuel, Beckman Research Institute, City of Hope National Medical Center, Duarte, California, USA
-Dr. David Carter, Oxford Brookes University, Oxford, UK
 

Selected publications

1-Fontana F, Moretti RM, Raimondi M, Marzagalli M, Beretta G, Procacci P, Sartori P, Montagnani Marelli M, Limonta P (2019). δ-Tocotrienol induces apoptosis, involving endoplasmic reticulum stress and autophagy, and paraptosis in prostate cancer cells.
Cell Prolif. e12576. doi: 10.1111/cpr.12576. 

2- Marzagalli M, Moretti RM, Messi E, Montagnani Marelli M, Fontana F, Anastasia A, Bani MR, Beretta G, Limonta P (2018). Targeting melanoma stem cells with the Vitamin E derivative δ-tocotrienol.
Sci Rep. 8:587. doi: 10.1038/s41598-017-19057-4.

3- Montagnani Marelli M, Marzagalli M, Moretti RM, Beretta G, Casati L, Comitato R, Gravina GL, Festuccia C, Limonta P (2016). Vitamin E δ-tocotrienol triggers endoplasmic reticulum stress-mediated apoptosis in human melanoma cells.
Sci Rep. 6:30502. doi: 10.1038/srep30502.

4- Marzagalli M, Montagnani Marelli M, Casati L, Fontana F, Moretti RM, Limonta P (2016). Estrogen receptor βin melanoma: from molecular insights to potential clinical utility.
Front Endocrinol. (Lausanne) 7:140. 

5- Limonta P, Montagnani Marelli M, Mai S, Motta M, Martini L, Moretti RM (2012). GnRH receptors in cancer: from cell biology to novel targeted therapeutic strategies.
Endocr Rev. 33:784-811.