New line of research against lung cancer

Researchers from the University of Barcelona (UB), together with oncologists from the Hospital Clínic de Barcelona, have analysed the most common neighbour cells in lung cancer, named fibroblasts, and identified specific alterations for each tumour subtype of the disease. The results of the study, published on the scientific journal Molecular Cancer Research of the American Association for Cancer Research, may facilitate the development of personalized therapies against the most common types of lung cancer.

The study was led by Jordi Alcaraz, associate professor in the Department of Physiological Sciences I at the Faculty of Medicine of the UB and researcher from the CIBER of Respiratory Diseases. Researchers from the August Pi i Sunyer Biomedical Research Institute (IDIBAPS), the Hospital Clínic and the Severo Ochoa Molecular Biology Centre (CSIC) also collaborated in the study.

Since 2010, the research group led by Jordi Alcaraz, located at the Unit of Biophysics and Bioengineering of the UB, have studied the role played by fibroblasts in tumour progression. Unlike healthy tissues, fibroblasts accumulate when there is a tumour. To date, it was thought that the accumulation was caused by the growth factors secreted by cancer cells. However, previous studies proved that fibroblasts are very sensitive to stiff microenvironments, characteristic of solid tumours.

The present study compared the cases in which accumulation was caused by biochemical elements, such as growth factors, and those in which it was due to tumour solidity. The samples that were studied were taken from fibroblasts of the most common lung cancer, the microcytic lung cancer, particularly from two of its subtypes: the adenocarcinoma and the squamous cell carcinoma.

Personalized therapies for each tumour

Results provided different answers depending on each type of tumour. “Unexpectedly, we found that the fibroblasts of the squamous cell carcinoma accumulate themselves in stiff microenvironments, not in non-rigid ones like the healthy lung, but they are quite insensible to growth factors. On the contrary, the fibroblasts of the adenocarcinoma do not benefit from stiff microenvironments, but they need many growth factors to proliferate and accumulate”, explains Jordi Alcaraz.

The study opens the door to profit the particular characteristics of each tumour subtype in order to design personalized therapies. “A recently published clinical study inhibited several pathways of growth factors. It was successful in the case of adenocarcinomas but unsuccessful in squamous cell carcinomas. Although it does not give any explanation, this clinical study could be linked with the results we got at the lab”, he points out.

A unique collection in Spain

In order to develop the study, the team led by Jordi Alcaraz, together with some oncologists from the Hospital Clínic de Barcelona, coordinated by Noemí Reguart, have created a unique collection of fibroblasts in Spain that includes samples of the main subtypes of lung cancer got from hospital’s patients.

The samples enabled the research team to go deeper into this line of research. “To date, studies were focused only on cancer cells. However, many studies have realized that cancer cells are not self-sufficient; they need to be helped by other cells to develop”, highlights Alcaraz. “Nowadays —he adds—, there is an increasing interest in developing new therapeutic strategies by knowing how cancer cells induce neighbour cells to work for them. In other words, if you are able to stop this inducement, cancer progression may be stopped too”.

In order to advance in this line of research, it is necessary to corroborate fibroblast specific alterations in other subtypes of lung cancer and to find out if cancer cells follow the behaviour pattern observed in fibroblasts.

Article reference

Marta Puig, Roberto Lugo, Marta Gabasa, Alícia Giménez, Adriana Velásquez, Roland Galgoczy, Josep Ramírez, Abel Gómez-Caro, Óscar Busnadiego, Fernando Rodríguez-Pascual, Pere Gascón, Noemí Reguart, Jordi Alcaraz. «Matrix Stiffening and Beta1 integrin Drive Subtype-specific Fibroblast Accumulation in Lung Cancer» Molecular Cancer Research. 2 de octubre de 2014. doi:10.1158/1541-7786.MCR-14-0155