Cancer Cachexia (CC) occurs in almost 80% of cancer patients and is the leading cause of death in about 20% of this population. The cause of the pathogenesis of cachexia is complex and involves different organs, cell types, hormones, cytokines/chemokines, growth factors, and interorgan crosstalk. During CC, several alterations occur in peripheral tissues, and the adipose tissue (AT) may be involved during the catabolic stimuli, such as increased lipid mobilization due to increased lipolysis, reduced lipogenesis and impairment of fat cell turnover. Moreover, AT inflammation plays an important role in the metabolic alterations of this organ. Macrophages are crucial drivers of tumor-promoting inflammation. Also, tumor-associated macrophages (TAMs) contribute to the tumor progression at different levels: by promoting genetic instability, nurturing cancer stem cells, supporting metastasis, and taming protective adaptive immunity. In response to signals from the extracellular environment, macrophages can be activated towards the pro-inflammatory (M1) or anti-inflammatory (M2) phenotype. Recent data suggest a protective role of macrophages in the loss of AT during cancer.
We will enroll colon cancer patients and controls with non-malignant diseases, undergoing surgery. We will collect AT during surgery, and tumor tissue after diagnosis to perform histomorphological analyses (cross-sectional area-CSA and percent of fibrosis) and immunohistochemistry to characterize macrophages M1/M2 population, identified by anti iNOS and anti CD163 antibodies, respectively. By CT-scan, we will calculate subcutaneous and visceral AT. The results of this project will provide useful indications on the different distribution of M1/M2 macrophages in subcutaneous, peritumoral AT and into the tumor tissue. Moreover, they will give information about the morphological difference of subcutaneous and peritumoral AT in a population of colorectal cancer patients.
Cancer cachexia is a disabling clinical condition, characterized by muscle wasting and progressive and generalized loss of AT. The loss of fat mass is strongly correlated with a risk of negative outcomes and short survival for these cancer patients. To date, is demonstrate that cachexia is associated with a higher mortality in cancer patients, compared to non-cachectic diagnosis. This project aims to characterize the macrophages populations (M1/M2) both within peripheral subcutaneous and into peritumoral AT, in colorectal cancer patients.
Our interest developing this project is to identify the predominant MF phenotype, in order to evaluate the impact of inflammation in different sites of AT during cancer cachexia. Moreover, from the results of this study it will also be possible to evaluate whether the loss of AT tissue occurs first in the peri-tumor site or into subcutaneous AT. For these purposes, the MF phenotype, and Cross-Sectional Area of adipocytes, into two types of AT, will be compared. Moreover, cancer cachectic, non-cachectic, and control group will be compared.
Nowadays, there are not clear data available on histomorphological characterization of inflammatory cells of the AT among cachectic cancer patients with and without cachexia. All the results deriving from these analyses can be considered preliminary and can be used in future to investigate the molecular mechanisms related to inflammation, underlying the loss of fat mass during cancer cachexia in a larger cohort of patients. The results of the project will provide useful indications to understand the behavior of inflammatory cells in AT during cachexia in humans, which is an almost unexplored field, although supported by data on experimental models. In this light could be possibly develop personalized nutritional and metabolic interventions aimed at modulating the inflammatory response and correcting AT wasting, thus improving post-operative recovery and long-term survival. Therefore, the innovation of the project is based on highlighting the distribution of specific inflammatory cells (macrophages), potentially involved in pathophysiology of cancer cachexia, and in the development of the clinical picture represented by AT derangement during this syndrome.