Rosário André (IPOLFG/ FCM-UNL) premiada pela EACR com o «Young investigator Award»

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Rosário André (IPOLFG/ FCM-UNL) premiada pela EACR com o «Young investigator Award»

Rosário André (IPOLFG/ FCM-UNL) premiada pela EACR com o «Young investigator Award»
Segunda, 07.01.2013

Rosário André was awarded with the «Young Investigator Award” by the EACR for her contribution for the understanding of the role of Interleukin-6 in tumor progression and metastatic development in solid tumors, in particular in breast cancer.

Rosário André is a Medical Oncology Fellow at Instituto Português de Oncologia de Lisboa Francisco Gentil and a PhD student at the Programa de Doutoramento em Medicina da Faculdade de Ciências Médicas da Universidade Nova de Lisboa, at Weill Cornell Medical College.

 

Abstract
INTERLEUKIN-6 EXPRESSION IN BONE MARROW-DERIVED CELLS REGULATES METASTATIC DISEASE

Maria do Rosário André1,2,3, Hector Peinado1, Min Zhang4, Jacqueline Bromberg4, David Lyden1,4

Weill Cornell Medical College, New York, USA
Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
Faculdade de Ciências Médicas da Univerdidade Nova de Lisboa Lisbon, Portugal
Memorial Sloan-Kettering Cancer Center, New York, USA 


Metastatic disease is the primary cause of cancer-related mortality, being responsible for more than 90% of cancer deaths. Improvements in cancer survival will only be tangible with a deeper knowledge and a better management of metastasis. In the past decade, there is a growing appreciation of the role of the cells comprising the cancer microenvironment in regulating metastatic progression. Identifying the crucial factors regulating these processes is the aim of this study. Clinically, elevated levels of the pro-inflammatory cytokine Interleukin-6 (IL-6) has been associated with advanced disease of different types. By using mice deficient in IL-6 we demonstrated that IL-6 knockout mice bearing orthotopically injected tumor cells (breast and melanoma) had a reduction in metastatic number and burden as compared to wild-type mice. Analysis of the pre-metastatic lungs and blood showed an increase of pSTAT3 activation in bone marrow derived cells (BMDC) during metastatic progression. Conditional overexpression of activated STAT3 demonstrated an increase in CD11b+Gr1+ cells in the lungs that was abrogated after IL-6 knockout. STAT3 activation was also evident in the bone-marrow microenvironment, and this was associated with an increase in IL-6 expression in BMDC. Notably, a restoration of metastatic growth of tumors was observed in IL-6 knockout mice transplanted with wild-type bone marrow. Our results reinforce the concept of inflammation as a principal player in metastatic development and demonstrate an association between IL-6 expression in bone-marrow derived cells and metastatic disease.