BONE STRUCTURAL AND VASCULAR CHANGES IN COLORECTAL CANCER-RELATED CACHEXIA

Cancer cachexia, developed as a secondary disease in cancer patients, is responsible of 20% of all cancer deaths. It is related to involuntarily loss of total body weight and muscle atrophy. In colorectal cancer (CRC) the incidence rate of cancer cachexia is 61%. There are many studies targeting to stop or reverse cachtetic muscle wasting yet to our knowledge there is no study that clarifies bone structural/vascular changes in CRC-cachexia. Thus, we aim to clarify if CRC with low bone metastasis rate, has effects on bone and to elucidate how cachexia changes bone in vascular and molecular levels. 8-week-old male BALBC mice ( n = 12) were divided into two groups as control (GroupC) and tumor (GroupT). GroupT was IP injected with 1×10 6 C26 cells while GroupC was injected with PBS. Animals were sacrificed on day26, and body weight without tumor (BW), spleen mass (SM), epididymal fat mass (EFM), muscle mass (MM) were compared. Muscle-atrophy-related gene expressions (MuRF1-Atrogin1) and serum IL-6 levels were checked to confirm cachexia. Ex-vivo µCT of femur bones was taken for bone structural assessments. To observe if CRC-cachexia affects bone-specific H-type endothelial vessels (CD31 Hi EMCN Hi ), immune-histochemical staining (IHCS) for CD31 and EMCN (with CD31, labels H-type-vessels) were done. The histological staining was done by hematoxylin-eosin (HE) staining. BW, MM and EFM were decreased, and SM was increased significantly in GroupT. MuRF-1 and Atrogin-1 expressions were significantly increased in GroupT. IL-6 serum level was also increased in GroupT however result was non-significant μCT assessment displayed bone-mineral-density (BMD) was significantly decreased in GroupT compared to GroupC IHCS demonstrated H-type-vessels in GroupT were the disrupted and barbed. In GroupT trabecular bone decrease was confirmed and an increased number of myeloid cells were observed by HE staining. In the literature, to our knowledge there is no study focused on bone structural/vascular changes in CRC-cachexia. Our results confirmed the mice were in cachectic state. The ex-vivo µCT assessments showed, CRC-cachexia is related to bone loss. The disrupted H-type-vessels in GroupT also showed CRC-cachexia disrupts the bone marrow vessels structure. The increase in myeloid cells in GroupT is correlated with μCT results and the decreased BMD, which may also be related to bone marrow inflammatory environment created by CRC-cachexia. Clarification of the mechanisms of CRC-cachexia on bone may show us new strategies for treatment of cachexia in clinics.