Relationship of inflammatory profile of elderly patients serum and senescence-associated secretory phenotype with human breast cancer cells proliferation: Role of IL6/IL8 ratio.

Aging is considered a systemic, chronic and low-grade inflammatory state, called "inflammaging", which has been contemplated as a risk factor for cancer development and progression in the elderly population. Cellular senescence is a multifactorial phenomenon of growth arrest and distorted function, which has been recognized as a contributor to aging. Senescent cells have an altered secretion pattern called Senescent Associated Secretory Phenotype (SASP), that comprise a complex mix of factors including cytokines, growth factors, chemokines and matrix metalloproteinases among others. The SASP secreted by accumulated senescent cells during old age has been related to local inflammation that leads to cellular transformation and therefore may be supporting the inflammaging process. Here, we evaluated if the pro-inflammatory profile within the serum obtained from elderly patients (EPS) was able to induce cellular proliferation in the breast cancer transformed cell line (MCF-7), in a similar way to the proliferation stimulated by the SASP obtained from WI-38 primary cells prematurely induced to senescence by oxidative stress (SIPS). At the same time, the participation of IL-6/IL-8 ratio was determined. Our results showed that not all the EPS increased MCF-7 proliferation. However, there was an interesting relationship between IL-6 and IL-8 concentrations, when the IL-6 was higher than IL-8. Similar results were found with SASP from SIPS-WI-38 on the MCF-7 proliferation. Although it is known that those cytokines are fundamental factors to induce proliferation; the occurrence of other components in the cellular microenvironment is necessary to carry out this effect.

[Involvement of phenotype secretor of senescent cells in the development of cancer, aging and the diseases associated with age]. / Participación del fenotipo secretor de las células senescentes en el desarrollo del cáncer, el envejecimiento y las enfermedades asociadas a la edad.

Cellular senescence is defined as the physiological program of terminal growth arrest; in mammals it is an important tumor-suppressor mechanism since it stops premalignant cell proliferation. However, senescence also contributes to the decline associated to aging and the development of several diseases. This is explained by the fact that senescent cells secrete diverse molecules, which compromise the cellular microenvironment, and altogether are referred as senescent-associated secretory phenotype (SASP). The SASP is composed by cytokines, chemokines, growth factors, proteases, etc., whose function is to maintain the antiproliferative state and promote senescent cell clearance by the immune system. Nevertheless, over time, and particularly during old age, SASP might stimulate proliferation and premalignant cell transformation. The multifunctional roles of SASP would depend on the cell type and their physiological nature. Therefore, relying on the biological context, SASP could be beneficial and participate in the repair and regeneration processes, or detrimental and induce degenerative pathologies and cancer.