Adipose stromal cells promote the transition of colorectal cancer cells toward a mesenchymal-like phenotype

Colon cancer progression is among the risks that increase with obesity. We have recently unveiled the molecular mechanism by which adipose tissue-released molecules, HGF and IL-6, make colorectal cancer (CRC) cells acquiring mesenchymal traits. Targeting of adipose-derived factors abrogate the metastatic potential of CRC stem cells (CR-CSCs) in obese patients

Novel insights into cancer stem cells targeting: CAR-T therapy and epigenetic drugs as new pillars in cancer treatment

Cancer stem cells (CSCs) represent the most aggressive subpopulation present in the tumor bulk retaining invasive capabilities, metastatic potential and high expression levels of drug efflux pumps responsible for therapy resistance. Cancer is still an incurable disease due to the inefficacy of standard regimens that spare this subpopulation. Selective targeting of CSCs is still an unmet need in cancer research field. Aberrant epigenetic reprogramming promotes the initiation and maintenance of CSCs, which are able to escape the immune system defense. Promising therapeutic approaches able to induce the selective inhibition of this stem-like small subset include immunotherapy alone or in combination with epigenetic compounds. These strategies are based on the specific expression of epitopes and/or epigenetic alterations present only in the CSC and not in the other cancer cells or normal cells. Thus, the combined approach utilizing CAR-T immunotherapy along with epigenetic probes may overcome the barriers of treatment ineffectiveness towards a more precision medicine approach in patients with known specific alterations of CSCs. In this perspective article we will shed new lights on the future applications of epi-immunotherapy in tumors enriched in CSCs, along with its potential side-effects, limitations and the development of therapy resistance

Colorectal cancer defeating? Challenge accepted!

Colorectal tumours are actually considered as aberrant organs, within it is possible to notice a different stage of cell growth and differentiation. Their origin is reported to arise from a subpopulation of tumour cells endowed with, just like the healthy stem cells, self-renewal and aberrant multi-lineage differentiation capacity likely to be called colorectal cancer stem cells (CCSCs). Cancer stem cells (CSCs) fate, since their origin, reflects the influences from their microenvironment (or niche) both in the maintenance of stemness, in promoting their differentiation, and in inducing epithelial-mesenchymal transition, responsible of CSCs dissemination and subsequent formation of metastatic lesions. The tumour cells heterogeneity and their immuno-response resistance nowadays probably responsible of the failure of the conventional therapies, make this research field an open issue. Even more importantly, our increasing understanding of the cellular and molecular mechanisms that regulate CSC quiescence and cell cycle regulation, self-renewal, chemotaxis and resistance to cytotoxic agents, is expected to eventually result in tailor-made therapies with a significant impact on the morbidity and overall survival of colorectal cancer patients

The miRNA Contribution in Adipocyte Maturation

Mesenchymal stem cells, due to their multipotent ability, are considered one of the best candidates to be used in regenerative medicine. To date, the most used source is represented by the bone marrow, despite the limited number of cells and the painful/invasive procedure for collection. Therefore, the scientific community has investigated many alternative sources for the collection of mesenchymal stem cells, with the adipose tissue representing the best option, given the abundance of mesenchymal stem cells and the easy access. Although adipose mesenchymal stem cells have recently been investigated for their multipotency, the molecular mechanisms underlying their adipogenic potential are still unclear. In this scenario, this communication is aimed at defining the role of miRNAs in adipogenic potential of adipose-derived mesenchymal stem cells via real-time PCR. Even if preliminary, our data show that cell culture conditions affect the expression of specific miRNA involved in the adipogenic potential of mesenchymal stem cells. The in vitro/in vivo validation of these results could pave the way for novel therapeutic strategies in the field of regenerative medicine. In conclusion, our research highlights how specific cell culture conditions can modulate the adipogenic potential of adipose mesenchymal stem cells through the regulation of specific miRNAs

Role of Type I and II interferons in colorectal cancer and melanoma

Cancer can be considered an aberrant organ with a hierarchical composition of different cell populations. The tumor microenvironment, including the immune cells and related cytokines, is crucial during all the steps of tumor development. In particular, type I and II interferons (IFNs) are involved in a plethora of mechanisms that regulate immune responses in cancer, thus balancing immune escape versus immune surveillance. IFNs are involved in both the direct and indirect regulation of cancer cell proliferation and metastatic potential. The mutational background of genes involved in IFNs signaling could serve as a prognostic biomarker and a powerful tool to screen cancer patients eligible for checkpoint blocking therapies. We herewith describe the latest findings regarding the contribution of IFNs in colorectal cancer and melanoma by researching their dual role as either tumor promoter or suppressor, in diverse tumor types, and microenvironmental context. We are reporting the most innovative and promising approaches of IFN-based therapies that have achieved considerable outcomes in clinical oncology practice and explain the possible mechanisms responsible for their failure

Distribution, function and predictive value of tumor-infiltrating γδ T lymphocytes

Although γδ T cells are known to exert both tumor-preventing and tumor-promoting activity, there is still little information on the functional characteristics and clinical significance of γδ T cells isolated from the tumor site. In a recent study, we have investigated the distribution of different γδ T-cell populations in melanoma and their impact on disease outcom

Involvement of caspase-3 and GD3 ganglioside in ceramide-induced apoptosis in Farber disease

Farber's disease (FD) is a rare genetic disorder caused by ceramidase deficiency, which results in ceramide accumulation in lung, liver, colon, skeletal muscle, cartilage, and bone. Although this disease has been symptomatically characterized, little is known about its molecular pathogenetic process. Because recent studies reported that ceramide accumulation induces GD3 ganglioside formation and apoptosis, we investigated, in tissue obtained via colonoscopy from seriously involved patients, the possible involvement of ceramide in FD colonocyte destruction. Histochemical and TUNEL analyses of paraffin-embedded sections revealed that 45 ± 4.3% of FD colonocytes showed morphological signs of apoptosis compared with the 8 ± 2.3% of constitutive epithelial cell death. Importantly, immunohistochemical study for pro-apoptotic factors showed that GD3 accumulation colocalized with active caspase-3 and cleaved K18 in FD colon tissue. These findings provide evidence for a role of the apoptotic ceramide pathway in the pathogenesis of FD

Estrogens and stem cells in thyroid cancer

Recent discoveries highlight the emerging role of estrogens in the initiation and progression of different malignancies through their interaction with stem cell (SC) compartment. Estrogens play a relevant role especially for those tumors bearing a gender disparity in incidence and aggressiveness, as occurs for most thyroid diseases. Although several experimental lines suggest that estrogens promote thyroid cell proliferation and invasion, their precise contribution in SC compartment still remains unclear. This review underlines the interplay between hormones and thyroid function, which could help to complete the puzzle of gender discrepancy in thyroid malignancies. Defining the association between estrogen receptors’ status and signaling pathways by which estrogens exert their effects on thyroid cells is a potential tool that provides important insights in pathogenetic mechanisms of thyroid tumors

Induction of annexin-1 during TRAIL-induced apoptosis in thyroid carcinoma cells

We investigated the expression of annexin-1 (ANXA1) in thyroid carcinoma cell lines and in thyroid cancers with a different degree of differentiation. The highest level of ANXA1 expression examined by Western blotting was detected in the papillary carcinoma cells (NPA) and in the follicular cells (WRO). On the other hand, the most undifferentiated thyroid carcinoma cells (ARO and FRO) presented the lowest level of ANXA1 expression. In surgical tissue specimens from 32 patients with thyroid cancers, we found high immunoreactivity for ANXA1 in papillary (PTC) and follicular (FTC) thyroid cancers while in undifferentiated thyroid cancers (UTC) the expression of the protein was barely detectable. Control thyroid tissue resulted positive for ANXA1. In summary, 70% of UTC examined weakly expressed ANXA1, whereas 65% of PTC or FTC specimens tested showed high expression of the protein. Thus ANXA1 expression may correlate with the tumorigenesis suggesting that the protein may represent an effective differentiation marker in thyroid cancer