Abstract
Metastasis involves the spread of cancer cells from the primary tumor to surrounding tissues and distant organs and is the primary cause of cancer morbidity and mortality. The aim of the study was the determination of change in molecular factors expression in primary kidney cancers (ccRCC) and metastatic sites. In total, 62 patients with RCC were enrolled in the study. The mRNA levels of molecular markers were studied by real-time PCR, and the content of the studied parameters was determined by Western blotting and ELISA. The features in the intracellular signal metabolites in the series of normal renal parenchyma, tumor tissue of localized, disseminated kidney cancer and metastatic tissue were studied. A decrease in some indicators in the tissue of the metastatic lesion was noted. Protein products of transcription factors HIF-1, CAIX, PTEN and activated AKT kinase, as well as expression of the VEGFR2 receptor and m-TOR protein kinase were revealed to be reduced in the metastatic sites. In addition, some indicators increased in metastasis: the protein levels of NF-κB p 50, NF-κB p 65, HIF-2, VEGF, VEGFR2, m-TOR and mRNA of HIF-1, CAIX, PTEN and PDK. There were indicators with multidirectional changes. HIF-1, CAIX, PTEN, VEGFR2 and m-TOR mRNA: VEGFR2, m-TOR, HIF-1, CAIX, PTEN and PDK had an opposite change in protein content and mRNA level. PTEN loss resulted in the downstream activation of AKT/mTOR signaling in secondary cancer lesions and determined the overall ccRCC patient’s survival. The AKT/mTOR signaling cascade activation was found in the primary kidney tumors. The PTEN content and mRNA level were correlated with total AKT, GSK-3β, the 70S 6 kinases and AKT expression.
Highlights
Metastasis involves the spread of cancer cells from the primary tumor to surrounding tissues and to distant organs and is the primary cause of cancer morbidity and mortality [1]
In a tumor of localized kidney cancer, an increase in the level of transcription factors was observed compared with normal renal parenchyma
The increase in the transcription factors expression was accompanied by the high values of the growth factor VEGF, whose level was 5.2 times higher than in the normal kidney parenchyma (Table 2)
Summary
Metastasis involves the spread of cancer cells from the primary tumor to surrounding tissues and to distant organs and is the primary cause of cancer morbidity and mortality [1]. The metastatic cascade includes the cancer cells detaching from the primary tumor, extravasation at distant capillary beds and invasion of distant organs [2]. Several hypotheses have been advanced to explain the origin of cancer metastasis. These involve an epithelial–mesenchymal transition, an accumulation of mutations in stem cells, a macrophage facilitation process and a macrophage origin involving either transformation or fusion hybridization with neoplastic cells. Metastases are responsible for the vast majority of cancer-related deaths. Tumor cells can become invasive early during cancer progression, metastases formation typically occurs as a late event [2,3]
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