Dr Elena Rainero

Dr Elena RaineroLecturer
Department of Biomedical Science
The University of Sheffield
Western Bank
Sheffield
S10 2TN
United Kingdom

Room: B2-04 Florey building
Telephone: +44-(0)114 222 3696
Email: e.rainero@sheffield.ac.uk

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Cell Biology and Cancer


General

Brief career history

  • 2016- present: Lecturer, The University of Sheffield (UK)
  • 2015–2016: Research Fellow, The University of Sheffield (UK)
  • 2009–2015: Post-doctoral researcher, the Beatson Institute for Cancer Research, Glasgow (UK)

Education

  • 2010: PhD in Human Biotechnology, University of Piemonte Orientale, Novara (Italy)
  • 2006: Master Degree in Medical and Pharmaceutical Biotechnology, 110/110 cum laude, University of Piemonte Orientale, Novara (Italy)
  • 2004: Bachelor Degree in Biotechnology, 110/110 cum laude, University of Piemonte Orientale, Novara (Italy)

Research interests

My group is interested in understanding the role of extracellular matrix internalisation in cell migration and invasion. The extracellular matrix (ECM) is a complex network of secreted proteins that, beyond providing physical support to organs and tissues, regulates many cell functions, including proliferation, polarity, migration and oncogenic transformation. Our aims are to understand the basic molecular events regulating ECM endocytosis, as well as how ECM uptake impinges on cell migration and invasion in complex 3D environments.

In the news:


ResearchGate


Full publications

Research

Extracellular matrix internalisation in breast cancer invasion

The extracellular matrix (ECM) is a complex network of secreted proteins which not only provides tissue support, but is also involved in the control of several cell functions, including migration and oncogenic transformation. The tumour microenvironment has a pivotal role in modulating cancer initiation, progression and metastasis, while cancer cells in turn modify the composition and properties of the ECM, demonstrating a bi-directional interaction between tumour and stroma. Our research addresses cell-ECM interaction from a novel and exciting angle, investigating how the internalisation of ECM components control breast cancer cell invasion.

Fugure 1

Using a combination of different approaches, we aim at characterising how ECM internalisation controls cancer cell migration and invasion in 2 dimensions (2D), 3 dimensions (3D) and in vivo systems.

Extracellular matrix internalisation in epithelial remodelling

Most of our organs are built from epithelial cells. They are supported extracellularly by a complex network of secreted proteins collectively known as extracellular matrix (ECM). The ECM is commonly viewed as “dead space” that provides a static scaffold for organ shape and acts as an obstacle for migrating cells. However, new data strengthen the idea that there is a dynamic interplay between cells and the ECM, which actively orchestrates how cells and organs acquire their shape. Therefore, a better understanding of how cells dynamically remodel their ECM environment and how the cell-ECM interplay contributes to epithelial remodelling will shed new light on fundamental mechanisms underlying the shaping of organs.

Figure 2

The mammary gland has a tree-like structure, whereby a single monolayer of epithelial cells surrounds the lumen of the ducts. The formation of new branches, or branching morphogenesis, is controlled by hormones and growth factors, including Hepatocyte Growth Factor (HGF). Moreover, the extracellular matrix (ECM) has been shown to have a key role in this process. Our data indicate that, upon HGF stimulation of normal mammary epithelial cells (MECs), tubule formation is associated with ECM remodelling and uptake, suggesting that ECM endocytosis might contribute to branching morphogenesis.

We aim at characterising the endocytic pathway(s) responsible for ECM uptake, focusing on the integrin family of ECM receptors, and assessing the contribution of ECM uptake to branching morphogenesis in 3D environments

Funding

  • Biochemical Society – Eric Reid Fund for Methodology (2016)
  • Royal Society - Research Grant (2016)
Teaching

Undergraduate and postgraduate taught modules

Level 3:

  • BMS349 Extended Library Project
  • BMS369 Laboratory Research Project
Opportunities

Postgraduate PhD studentship

Supervisor: Dr Elena Rainero

Funding status: Competition funded project European/UK students only

This project is eligible for a department scholarship. These scholarships are awarded on a competitive basis – find out more on our funding webpage.

This project is also open to self funded students

Project Description

This project focuses on the interaction between cancer cells and the tumour microenvironment, analysing the role of the extracellular matrix (ECM) modifying enzyme ADAMTS5 in ovarian cancer cell invasive migration. In particular, we will dissect how ADAMTS5 protein is upregulated in ovarian cancer cells and the molecular mechanisms through which the cleavage of the ADAMTS5 substrate versican promotes cancer cell invasion. Ovarian cancer is the most lethal gynaecological malignancy.

Mostly because of late stage diagnosis, the 5-year survival rate is <30%. The major cause of death is associated with the presence of therapy-resistant metastasis. Given the fact that >70% of ovarian cancers are diagnosed at late stage, it is essential to understand what the molecular mechanisms controlling metastasis formation are in order to develop novel strategies for the maintenance of this deadly disease. The tumour microenvironment, including the ECM, has a pivotal role in modulating cancer initiation, progression and metastasis. In particular, Versican (VCAN), a proteoglycan of the lectican family, has been shown to be upregulated in brain tumours, melanomas, osteosarcomas, lymphomas, breast, prostate, colon, lung, pancreatic, endometrial, oral and ovarian cancers and high VCAN expression correlates with reduced overall survival in ovarian cancer patients. VCAN is cleaved by a family of zinc-dependent metalloproteases, A Disintegrin And Metalloproteinase Domain with TromboSpondin type I module (ADAMTS), composed of 19 members of secreted proteases, including ADAMTS5. ADAMTS5 has been shown to increase cell invasive potential in glioblastoma, lung cancer, colon cancer and laryngeal cancer cells. Vesicular trafficking is essential for the polarised distribution of transmembrane receptors and secreted molecules and it is controlled by Rabs, small GTPases of the Ras family.

It is not surprising that alterations in Rab expression and function have been associated with cancer. In particular, epithelial specific Rab25, a member of the Rab11 family, has been shown to promote ovarian cancer cell migration and invasion. Consistent with this, high Rab25 expression correlates with poor prognosis in ovarian cancer. Preliminary data from the lab indicate that Rab25 induces ADAMTS5 expression, and the catalytic activity of ADAMTS5 is required for Rab25-induced cancer cell migration and invasion through 3D environments.

Therefore, we hypothesise that Rab25-expressing ovarian cancer cells upregulate ADAMTS5 expression when in contact with fibroblast-generated ECM. This in turn stimulates their migratory and invasive ability, eventually promoting metastasis formation. This project specifically aims at answering the following questions:

  • How does Rab25 induce ADAMTS5 expression?
  • How does ADAMTS5 promote migration of ovarian cancer cells?
  • Does ADAMTS5 inhibition prevent high grade serous ovarian cancer cell invasion?

Despite the incidence and mortality of ovarian cancer, the mechanisms controlling metastasis are not fully understood. The outcome of this project will deepen our understanding of the interplay between cancer cells and the ECM, highlighting whether ADAMTS5 can represent a novel target for the development of new ovarian cancer therapies.

Keywords: Cancer / Oncology, Cell Biology / Development

Contact information

For informal enquiries about the project or application process, please feel free to contact me.

To find out more about this project and how to apply see our PhD opportunities page:

PhD Opportunities

Selected publications

Journal articles