Lung cancer is the most common tumor worldwide. Every year approximately 30,000 new cases are detected in Spain. One of the factors marking the prognosis of this disease is its ability to cause metastasis in bone. Scientists at the Center for Applied Medical Research (CIMA) and at the Clínica Universidad de Navarra have discovered new mechanisms which advance this process.

“Our work studies the role of part of the immune system, specifically the complement system, in the capacity of the lung cancer cell to migrate and invade bone. And we have proven that the expression of a complement system receptor called C5aR promotes bone metastasis of the tumor cells”, explained Dr. Rubén Pío and Dr. Fernando Lecanda, director and main researcher, respectively, of the Solid Tumor Program at CIMA, who coordinate the study. As explained by Dr. Daniel Ajona, another of the main authors of the work, “by inhibiting this protein in the laboratory we have found that the migratory capacity of the tumor cells to bone is reduced. Therefore, this strategy is suggested as a very promising proposal for clinical application”.

The results have been confirmed in experimental lung cancer models and in biological samples at the Hospital General Universitario de Valencia. “The preliminary data obtained in patient samples suggest that when there is greater expression of this receptor in the primary tumor, the prognosis for the patient is worse, that is to say, it progresses faster or the patient dies sooner. Likewise, by retrospectively revising the samples from patients with metastasis we have found that they have higher expression of the C5aR receptor”, stated Dr. Lecanda. Now that the results of metastasis to bone have been confirmed, the researchers propose to study its implication in the capacity to invade other organs apart from bone.

The work of the University of Navarra is part of a research project integrated in CIBERONC, and has been carried out thanks to the funding of the Asociación Española Contra el Cáncer (AECC), and other organizations. The results have been published in the latest issue of the American Journal of Respiratory and Critical Care Medicine.

Sistema inmune contra el cáncer

The complement system is an element of the immune system which is activated as the first line of defense against the presence of foreign elements in the organism. According to Dr. Pío, “The complement system is part of the defense mechanism against cancer. Nevertheless, the tumors adapt and become resistant to its effects, which leads to danger: the complement system continues to function and promotes chronic inflammation, thereby favoring the development of the tumors”.

Previous studies by the CIMA researchers showed that the inhibition of the C5aR receptor, combined with immunotherapy, can be a therapeutic target for cancer. “We now wish to confirm these results in other types of lung cancer, such as small cell lung cancer . We are also working on new markers will allow us to predict which patients may benefit from this therapy in order to personalize the treatment as much as possible”, the researchers state.

 

Bibliographical reference

Am J Respir Crit Care Med. 2018 May 1;197(9):1164-1176. doi: 10.1164/rccm.201703-0660OC.