0000000000190137
AUTHOR
Tiziana Apuzzo
Additional file 1: Figure S1. of Combined platelet-rich plasma and lipofilling treatment provides great improvement in facial skin-induced lesion regeneration for scleroderma patients
showing AD-MSCs from both healthy subjects and SSc patients with increased levels of CD271 expression. Representative dot plot showing the expression of CD271 corresponding isotype match control in freshly isolated SVF and long-term propagated AD-MSCs from healthy subjects (upper panels) and SSc patients (lower panels), performed by flow cytometry. (PDF 205Â kb)
Elimination of quiescent/slow-proliferating cancer stem cells by Bcl-XL inhibition in non-small cell lung cancer
Lung cancer is the most common cause of cancer-related mortality worldwide, urging the discovery of novel molecular targets and therapeutic strategies. Stem cells have been recently isolated from non-small cell lung cancer (NSCLC), thus allowing the investigation of molecular pathways specifically active in the tumorigenic population. We have found that Bcl-XL is constantly expressed by lung cancer stem cells (LCSCs) and has a prominent role in regulating LCSC survival. Whereas chemotherapeutic agents were scarcely effective against LCSC, the small molecule Bcl-2/Bcl-XL inhibitor ABT-737, but not the selective Bcl-2 inhibitor ABT-199, induced LCSC death at nanomolar concentrations. Differen…
Cancer Stem Cells Sensitivity Assay (STELLA) in Patients with Advanced Lung and Colorectal Cancer: A Feasibility Study.
Background Cancer stem cells represent a population of immature tumor cells found in most solid tumors. Their peculiar features make them ideal models for studying drug resistance and sensitivity. In this study, we investigated whether cancer stem cells isolation and in vitro sensitivity assay are feasible in a clinical setting. Methods Cancer stem cells were isolated from effusions or fresh cancer tissue of 23 patients who progressed after standard therapy failure. Specific culture conditions selected for immature tumor cells that express markers of stemness. These cells were exposed in vitro to chemotherapeutic and targeted agents. Results Cancer stem cells were extracted from liver metas…
CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis.
SummaryCancer stem cells drive tumor formation and metastasis, but how they acquire metastatic traits is not well understood. Here, we show that all colorectal cancer stem cells (CR-CSCs) express CD44v6, which is required for their migration and generation of metastatic tumors. CD44v6 expression is low in primary tumors but demarcated clonogenic CR-CSC populations. Cytokines hepatocyte growth factor (HGF), osteopontin (OPN), and stromal-derived factor 1α (SDF-1), secreted from tumor associated cells, increase CD44v6 expression in CR-CSCs by activating the Wnt/β-catenin pathway, which promotes migration and metastasis. CD44v6− progenitor cells do not give rise to metastatic lesions but, when…
Microenvironment in neuroblastoma: isolation and characterization of tumor-derived mesenchymal stromal cells
Background It has been proposed that mesenchymal stromal cells (MSCs) promote tumor progression by interacting with tumor cells and other stroma cells in the complex network of the tumor microenvironment. We characterized MSCs isolated and expanded from tumor tissues of pediatric patients diagnosed with neuroblastomas (NB-MSCs) to define interactions with the tumor microenvironment. Methods Specimens were obtained from 7 pediatric patients diagnosed with neuroblastoma (NB). Morphology, immunophenotype, differentiation capacity, proliferative growth, expression of stemness and neural differentiation markers were evaluated. Moreover, the ability of cells to modulate the immune response, i.e. …
Additional file 2: Figure S2. of Combined platelet-rich plasma and lipofilling treatment provides great improvement in facial skin-induced lesion regeneration for scleroderma patients
showing AD-MSCs from SSc patients with decreased levels of mesenchymal stem cell markers. Representative dot plot showing the expression of CD44, CD90, CD271, CD29, CD73, and CD9 in AD-MSCs from healthy subjects (upper panels) and SSc patients (lower panels). Small boxes show isotype match control staining. (PDF 316Â kb)
Targeting chemoresistant colorectal cancer via systemic administration of a BMP7 variant
Abstract Despite intense research and clinical efforts, patients affected by advanced colorectal cancer (CRC) have still a poor prognosis. The discovery of colorectal (CR) cancer stem cell (CSC) as the cell compartment responsible for tumor initiation and propagation may provide new opportunities for the development of new therapeutic strategies. Given the reduced sensitivity of CR-CSCs to chemotherapy and the ability of bone morphogenetic proteins (BMP) to promote colonic stem cell differentiation, we aimed to investigate whether an enhanced variant of BMP7 (BMP7v) could sensitize to chemotherapy-resistant CRC cells and tumors. Thirty-five primary human cultures enriched in CR-CSCs, includ…
Combined platelet-rich plasma and lipofilling treatment provides great improvement in facial skin-induced lesion regeneration for scleroderma patients.
Background The use of stem cells, including mesenchymal stem cells (MSCs), for regenerative medicine is gaining interest for the clinical benefits so far obtained in patients. This study investigates the use of adipose autologous tissue in combination with platelet-rich plasma (PRP) to improve the clinical outcome of patients affected by systemic sclerosis (SSc). Methods Adipose-derived mesenchymal stem cells (AD-MSCs) and PRPs were purified from healthy donors and SSc patients. The multilineage differentiation potential of AD-MSCs and their genotypic–phenotypic features were investigated. A cytokine production profile was evaluated on AD-MSCs and PRPs from both healthy subjects and SSc pat…
IL4 Primes the Dynamics of Breast Cancer Progression via DUSP4 Inhibition
Abstract The tumor microenvironment supplies proinflammatory cytokines favoring a permissive milieu for cancer cell growth and invasive behavior. Here we show how breast cancer progression is facilitated by IL4 secreted by adipose tissue and estrogen receptor–positive and triple-negative breast cancer cell types. Blocking autocrine and paracrine IL4 signaling with the IL4Rα antagonist IL4DM compromised breast cancer cell proliferation, invasion, and tumor growth by downregulating MAPK pathway activity. IL4DM reduced numbers of CD44+/CD24− cancer stem-like cells and elevated expression of the dual specificity phosphatase DUSP4 by inhibiting NF-κB. Enforced expression of DUSP4 drove conversio…
A perspective analysis: microRNAs, glucose metabolism, and drug resistance in colon cancer stem cells
Metabolism sustains the stemness of Cancer Stem Cells (CSCs), affecting, in turn, tumor heterogeneity, metastatic potential, and therapy resistance. Therefore, it is appealing to target CSCs metabolism as a new therapeutic approach. Consequently, we paid considerable attention to the anti-apoptotic microRNA miR-483-3p, that we reported being regulated by glucose metabolism in liver cancer cells. We investigated the therapeutic potential of targeting miR-483-3p by using the anti-glucose metabolism 2-deoxyglucose (2-DG) molecule in tumor Xenograft mouse model originating from two different Colon-Cancer Stem Cell lines (CCSC lines). We show that 2-DG treatment does not affect CCSCs during tumo…
Accumulation of Circulating CCR7+ Natural Killer Cells Marks Melanoma Evolution and Reveals a CCL19-Dependent Metastatic Pathway
Abstract Immune checkpoint blockade therapy has changed prognoses for many melanoma patients. However, immune responses that correlate with clinical progression of the disease are still poorly understood. To identify immune responses correlating with melanoma clinical evolution, we analyzed serum cytokines as well as circulating NK and T-cell subpopulations from melanoma patients. The patients' immune profiles suggested that melanoma progression leads to changes in peripheral blood NK and T-cell subsets. Stage IV melanoma was characterized by an increased frequency of CCR7+CD56bright NK cells as well as high serum concentrations of the CCR7 ligand CCL19. CCR7 expression and CCL19 secretion …
ΔNp63 drives metastasis in breast cancer cells via PI3K/CD44v6 axis
P63 is a transcription factor belonging to the family of p53, essential for the development and differentiation of epithelia. In recent years, it has become clear that altered expression of the different isoforms of this gene can play an important role in carcinogenesis. The p63 gene encodes for two main isoforms known as TA and ΔN p63 with different functions. The role of these different isoforms in sustaining tumor progression and metastatic spreading however has not entirely been clarified. Here we show that breast cancer initiating cells express ΔNp63 isoform that supports a more mesenchymal phenotype associated with a higher tumorigenic and metastatic potential. On the contrary, the ma…
Additional file 1: of Microenvironment in neuroblastoma: isolation and characterization of tumor-derived mesenchymal stromal cells
Figure S1. Immunophenotype characterization of NB-MSCs. Immunophenotype characterization of NB tissue derived-MSC from a representative sample. NB-MSCs are gated on physical parameter (FSC and SSC). Surface marker expression of NB-MSC are reported in overlay histograms with light grey peaks representing negative control by isotype-matched, nonreactive fluorochrome-conjugated antibodies. Dark grey peaks represent positive cells. Histograms of surface marker expression are typical of MSC being positive for CD105, CD73, CD90 and HLA-I and negative for HLA-DR, CD31, CD14, CD45 and CD34. (JPG 132 kb)
Additional file 2: of Microenvironment in neuroblastoma: isolation and characterization of tumor-derived mesenchymal stromal cells
Figure S2. Flow cytometry profiles of selected stemness markers in BM-MSCs and NB-MSCs. (Left panel) representative scatter plots of SSC vs FSC of BM-MSC and NB-MSC cells. (Right panel) indicative flow cytometry profiles of selected markers in BM-MSC and NB-MSC samples. Dotted grey light histograms represent the relative isotype matched control. (JPG 157 kb)
Additional file 3: of Microenvironment in neuroblastoma: isolation and characterization of tumor-derived mesenchymal stromal cells
Figure S3. Flow cytometry analysis in BM-MSCs and NB-MSCs. Flow cytometry analysis of cell cycle in BM-MSCs and NB-MSCs. Plots show the percentage of cells in sub-G0 phase (white box), G0-G1 phase (grey box), S phase (pink box) and G2-M phase (light yellow box). (JPG 132 kb)