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Centre for Cancer Biomarkers CCBIO

Transcapillary Exchange

The research focus of Rolf Reed's group is on the how the extracellular matrix participates in determining the properties of the tumors and how this in turn is reflected in growth and metastasis. Additional foci have been on how collagen binding integrins influence these properties and also how tumor hypoxia does the same.

Portrait photo.
Photo:
Ingvild Festervoll Melien Illustration: Gaute Hatlem/Eli Vidhammer

Projects

Projects have focused on:

• The interaction between the collagen binding α11 integrin and integrin α11β1 to determine biophysical tumor properties, growth and metastasis

• Effect of hyperbaric oxygen treatment on tumor growth and properties as well as metastasis and metastatic profile

• Collaboration with the Akslen and Gullberg groups on the use of monoclonal antibodies against human α11 integrin as a biomarker for human cancer

Important results

The long term project is on the in vivo interaction between collagen binding integrins, in particular α11β1 and the αVβ3 which is a non-collagen binding integrin, and which seems to take over the role of the collagen binding β1-integrins. The project investigates the properties of different tumor cell lines in mice with deletion of either one of these integrins. The studies demonstrate that both the matrix and the specific cell lines will affect tumor properties. 

One study (published 2017) used four different cell lines that were exposed to normoxia or hypoxia alone or in combination with Transforming Growth Factor -β1 or Jagged-1 that are known to induce EMT, were investigated one by one. Importantly, it was found that one factor alone induced mesenchymal morphology in isolated breast cancer cells, but did not induce full EMT.

Another study published in 2017 is an extension of a previous study which demonstrated that hyperbaric oxygen treatment (HBOT) attenuated tumor growth and shifted the phenotype from mesenchymal to epithelial (MET) in the DMBA-induced mammary tumor model. The new study investigated the effect of HBOT on tumor growth, angiogenesis, chemotherapy efficacy and metastasis in a triple negative (MDA-MB-231) and a triple positive (BT-474) breast cancer model in NOD/SCID female mice. HBOT significantly suppressed tumor growth in both the triple positive and negative tumors, and decreased proliferation, the number metastases and reduced expression of N-cadherin, Axl and collagen type I.

The similar suppressive effect of HBOT on the two cell lines indicates that they share a common oxygen dependent anti-tumor mechanism. Notably, HBOT also reduced the number of metastatic lesions in the triple negative model.

Future plans

The group will continue to study the interaction between the matrix and cancer cells in determining the tumor’s properties as well as growth and metastatic profile. They will also investigate the effect of hyperbaric oxygen further, and initiate the use of PdX models in their studies.

Current challenges in the field

The role of oxygen including hyperbaric oxygen is an important challenge, as well as collagen fiber network and its role in tumor biology.

2016 Spring Interview

The Rolf Reed Group is focusing on research that leads to better insight of the tumor stroma and its dynamic properties, with the goal of altering therapeutic principles of solid tumors.

Could you tell us about your research on transcapillary exchange - what does it really mean?

"Transcapillary exchange describes the transport and transport processes taking place at the smallest blood vessels in the body, the microcirculation. This is where the nutrients are delivered by the arterial blood and then transported across the microvessels to reach the cells of the tissue while waste products are removed from the cells across the microcirculation and leave the tissue via the venous blood. Transcapillary exchange is determined by the pressure across the microvessels as well as the properties of these vessels. Our research has a particular focus on how the tissue via its structural molecules also can influence this transport by altering the biophysical properties of the tissue and thereby the pressures responsible for this transport. An immediate problem in cancers is a high tissue pressure that limits transport across the microvessels which also limits the delivery of cytostatic agents from the blood to the tumor. Our research is aimed at understanding what generates this high pressure and how the tumor microenvironment can be modified to enhance the transport."

How would you describe your findings so far?

"We have especially been working on the role of the collagen binding cellular receptors, the integrins, and how altered integrin-expression, i.e. collagen binding properties, will modify the microenvironment of the tumor and also the biophysical properties involved in transcapillary transport."

What groups of cancer patients is your work concentrated on?

"The research we are performing is not focused on a particular group of cancers. It is better characterized as “underpinning” since the aim is to understand basic mechanisms of transport across the microvascular barrier and its interaction with tissue stroma in general and with specific emphasis on the events that are altered in cancers."

PubMed Publications