Tendency to conversion from state of chronic inflammation to malignancy is a tumor characteristic trait, which encourages progression to its metastatic stage.. The inflammatory cells maintaining in the tumor inaugurate a communication with cancer cells and become tumor-fostering cells. Epithelial-mesenchymal transition (EMT) is a program supporting malignant cells during switch phenotype into metastatic form, providing looseness of cell-cell adherence and strengthens migratory or invasive features. EMT-undergone tumor cells become more aggressive and resistant to apoptosis. Additionally, malignant cells can be stimulated to manufacture proinflammatory factors throughout EMT program. Chronic inflammation is responsible for EMT induction in malignancies. Developed tumors induce inflammatory response through excretion of cytokines, chemokines and growth factors, which recruit populations of infiltrating immune cells straight to the tumor microenvironment. The inflammatory reaction potentially exerts tumor control, but instead it can be intercepted by the tumor to stimulate its own development in direction to metastatic form. Our study confirmed that SDF-1 chemokine and its receptors, CXCR4 and CXCR7 may participate in initiation of metastases formation and EMT process.

Resistance to systemic therapy is one of the hallmarks of renal cell carcinoma (RCC). Recently, TOLLIP has emerged as a possible driver of autophagy and chemoresistance. We explored the relationship between primary and metastatic RCC tumor characteristics, patient survival, and TOLLIP expression. The tissue microarrays cohort contained 95 cores of the primary tumor, matched metastases, and matched adjacent tissues derived from 32 RCC patients. TOLLIP expression in tumor samples was evaluated using the H-score. All examined samples showed cytoplasmic TOLLIP expression, with a median value of 100 in primary tumors, 107.5 in metastases, and 220 in the control group. The expression was significantly higher in the normal adjacent tissues compared to primary or metastatic RCC (p < 0.05). We found a positive correlation between expressions of TOLLIP in the primary tumor and its metastases (p < 0.05; k = 0.48). TOLLIP expression significantly correlates with a lower overall survival rate (p = 0.047). TOLLIP functions as a ubiquitin-LC3 adaptor in the intracellular pathway associated with autophagy. Relative TOLLIP overexpression may augment autophagy-related signaling, limiting susceptibility to therapy. The blockade of TOLLIP physiological function seems to be a promising approach to overcoming resistance to systemic therapy.