Principal Investigator: Professor Maria Alfonsina Desiderio

Members: Dr Paola Bendinelli, Dr Emanuela Matteucci, Dr Paola Maroni (visiting researcher from IRCCS Galeazzi Orthopaedic Institute); Dr. Alessia Locatelli

 

The group’s research activity is focused on:

The research interest of this Laboratory deals with the growth of hepatocarcinoma and mammary carcinoma as well as with bone metastatic process of breast carcinoma. Bone microenvironment is influenced by metastatic cell engraftment, and also by biological signals derived from primary tumor becoming hospitable for metastasis growth. Hepatocyte growth factor (HGF) is one of these signals acting at local and systemic levels. HGF binds to Met receptor present on metastatic and supportive cells of bone microenvironment, allowing the formation of a network of metastasis/stroma interactions. Osteolysis represents the worst clinical complications, leading to patient death.

 

The research activities of the Laboratory of Molecular Pathology regards:

-molecular and cellular mechanisms that favor the bone tropism and the development of osteolytic metastases from breast cancer;

-role played by biological (HGF) and physical (hypoxia) stimuli in the invasive growth and in bone metastases formation;

-epigenetic regulation of gene expression, responsible for the plasticity of tumor cells and for differentiation of adipose tissue derived stem cells ;

-interaction of tumor cells with stromal cells.

The identification of the molecular mechanisms responsible for the growth and progression of metastasis is essential for the development of new and more effective therapies.

 

The research includes in in vitro and in vivo studies.

In vitro studies. Human cell lines of breast cancer with marked bone tropism are available. These cells are used for the study of gene expression, nuclear signaling pathways and invasive capacity in response to biological and physical stimuli.

In vivo studies. We prepared a murine xenograft model of osteolytic bone metastases using 1833 cells engineered with a construct containing GFP and luciferase, that allow to evaluate in vivo the formation and growth of metastases using Optical Imaging technology. This model permits to test the efficacy of pharmacological and genetic inhibitors in reducing the formation of bone metastases.

Human metastasis. The results of the in vitro studies are corroborated by observations made on biopsies of breast cancer and the corresponding bone metastasis. These samples are obtained in the context of a collaboration with the Galeazzi Orthopaedic Institute, one of the two Italian centers in which surgery on patients with bone metastases are performed.

 Recent/relevant Publications

1) Matteucci E, Maroni P, Luzzati A, Perrucchini G, Bendinelli P, Desiderio MA. Bone metastatic process of breast cancer involves methylation state affecting E-cadherin expression through TAZ and WWOX nuclear effectors. Eur J Cancer. 2013, 49:231-244. (IF: 5.536)

2) Bendinelli P, Maroni P., Matteucci E., Luzzati A., Perrucchini G., Desiderio MA. "HIF-1 is activated by TAZ versus Wwox in hypoxic microenvironment of bone metastasis from breast cancer” in press 2013, DOI: 10.1016/j.ejca.2013.03.002. (IF: 5.536)

3) Maroni P, Brini AT, Arrigoni E, de Girolamo L, Niada S, Matteucci E, Bendinelli P, Desiderio MA. Chemical and genetic blockade of HDACs enhances osteogenic differentiation of human adipose tissue-derived stem cells by oppositely affecting osteogenic and adipogenic transcription factors. Biochem Biophys Res Commun. 2012, 428:271-277. (IF: 2.484)

4) Maroni P, Matteucci E, Luzzati A, Perrucchini G, Bendinelli P, Desiderio MA. Nuclear co-localization and functional interaction of COX-2 and HIF-1alpha characterize bone metastasis of human breast carcinoma. Breast Cancer Res Treat. 2011, 129:433-450. (IF: 4.431)

5) Previdi S, Maroni P, Matteucci E, Broggini M, Bendinelli P, Desiderio MA. Interaction between human-breast cancer metastasis and bone microenvironment through activated hepatocyte growth factor/Met and beta-catenin/Wnt pathways. Eur J Cancer. 2010, 46:1679-1691. (IF: 5.536)

6) Bendinelli P, Matteucci E, Dogliotti G, Corsi MM, Banfi G, Maroni P, Desiderio MA. Molecular basis of anti-inflammatory action of platelet-rich plasma on human chondrocytes: mechanisms of NF-kappaB inhibition via HGF. J Cell Physiol. 2010, 225:757-766. (IF: 3.874)

7) Matteucci E, Bendinelli P, Desiderio MA. Nuclear localization of active HGF receptor Met in aggressive MDA-MB231 breast carcinoma cells. Carcinogenesis. 2009, 30:937-945. (IF: 5.702)

 

Contacts

Prof.ssa Maria Alfonsina Desiderio: tel. 02-50315334, fax 02-50315338, email: a.desiderio@unimi.it

Dott.ssa Paola Bendinelli:  tel. 02-50315335, email: paola.bendinelli@unimi.it

Dott.ssa Emanuela Matteucci: tel. 02-50315335; email: emanuela.matteucci@unimi.it

Dott.ssa Paola M. Maroni: tel. 02-50315335; email: paola.maroni@guest.unimi.it;  paola.maroni@grupposandonato.it