Platelets Promote Mitochondrial Uncoupling and Resistance to Apoptosis in Leukemia Cells: A Novel Paradigm for the Bone Marrow Microenvironment
Abstract
Here we report that leukemia cell lines and primary CD34+ leukemic blasts exposed to platelet rich plasma (PRP) or platelet lysates (PL) display increased resistance to apoptosis induced by mitochondria-targeted agents ABT-737 and CDDO-Me. Intriguingly, leukemia cells exposed to platelet components demonstrate a reduction in mitochondrial membrane potential (ΔΨM) and a transient increase in oxygen consumption, suggestive of mitochondrial uncoupling. Accompanying the ranolazine-sensitive increase in oxygen consumption, a reduction in triglyceride content was also observed in leukemia cells cul...
Source: Cancer Microenvironment - August 1, 2014 Category: Cancer & Oncology Source Type: research
Microparticles mediated cross-talk between tumoral and endothelial cells promote the constitution of a pro-metastatic vascular niche through Arf6 up regulation
Abstract
The tumor stroma plays an essential role in tumor growth, resistance to therapy and occurrence of metastatic phenotype. Tumor vessels have been considered as passive conducts for nutrients but several studies have demonstrated secretion of pro-tumoral factors by endothelial cells. The failure of anti-angiogenic therapies to meet expectations raised by pre-clinical studies prompt us to better study the cross-talk between endothelial and cancer cells. Here, we hypothesized that tumor cells and the endothelium secrete bio-active microparticles (MPs) participating to a functional cross-talk. We cha...
Source: Cancer Microenvironment - August 1, 2014 Category: Cancer & Oncology Source Type: research
T Cell Avidity and Tumor Immunity: Problems and Solutions
Abstract
A potent T cell response is an important component of durable anti-tumor immunity. The quality of the T cell response can, in-part, be measured by the avidity of the T cell for its tumor antigen-expressing target. While convention suggests that raising the avidity of the responding T cells may make for a more potent anti-tumor immune response, the threshold for effective tumor immunity remains unclear, as do some of the adverse effects of an inappropriately high avidity response. In this review, we discuss the relationship between T cell avidity and anti-tumor immunity, considering both experim...
Source: Cancer Microenvironment - August 1, 2014 Category: Cancer & Oncology Source Type: research
Small But Mighty: Microparticles as Mediators of Tumor Progression
Abstract
A wide spectrum of both normal and diseased cell types shed extracellular vesicles that facilitate intercellular communication without direct cell-to-cell contact. Microparticles (MPs) are a subtype of extracellular vesicles that participate in multiple biological processes. They carry abundant bioactive molecules including different forms of nucleic acids and proteins that can markedly modulate cellular behavior. MPs are involved in several hallmarks of cancer such as drug resistance, thrombosis, immune evasion, angiogenesis, tumor invasion and metastasis. Such MPs originate from either cancer...
Source: Cancer Microenvironment - August 1, 2014 Category: Cancer & Oncology Source Type: research
Extracellular Matrix Protein Laminin Induces Matrix Metalloproteinase-9 in Human Breast Cancer Cell Line MCF-7
Abstract
Studies on interaction of tumor cells with extracellular matrix (ECM) components showed increased extracellular protease activity mediated by the family of matrix metalloproteinases (MMPs). Here we studied the effect of human breast cancer cell line MCF-7-laminin (LM) interaction on MMPs and the underlying signaling pathways. Culturing of MCF-7 cells on LM coated surface upregulated MMP-9 expression as well as reduced tissue inhibitor of metalloproteinases-1 (TIMP-1) expression. LM induced MMP-9 expression is abrogated by the blockade of α2 integrin. Inhibitor studies indicate possible involve...
Source: Cancer Microenvironment - August 1, 2014 Category: Cancer & Oncology Source Type: research
Macrophage Infiltration in Tumor Stroma is Related to Tumor Cell Expression of CD163 in Colorectal Cancer
This study was conducted to evaluate the relationship between CD163 expression as a macrophage trait in cancer cells, and macrophage infiltration and its clinical significance in colorectal cancer. Immunostaining of CD163 and macrophage infiltration were evaluated in paraffin-embedded specimens, earlier analyzed for CD31, D2-40 and S-phase fraction, from primary tumors and normal colorectal mucosa of 75 patients with colorectal carcinoma. The outcomes were analyzed in relation to clinical-pathological data. CD163 expression was positive in cancer cells in 20 % of colorectal cancer patients and was related to advanced tumo...
Source: Cancer Microenvironment - August 1, 2014 Category: Cancer & Oncology Source Type: research
Detection of Estrogen-Independent Growth-Stimulating Activity in Breast Cancer Tissues: Implication for Tumor Aggressiveness
In this study, we analyzed the effects of individual breast cancer extracts by our original system using an estrogen-signal reporter cell line, MCF-7-E10, which we previously established. MCF-7-E10 cell line is stably transfected by an estrogen response element (ERE)-green fluorescent protein (GFP) gene; it expresses GFP when estrogen receptors (ERs) are activated by estrogen or growth factor signal-mediated ER phosphorylation. Using this cell line, we analyzed the comprehensive effects of factors derived from breast cancer tissues on ER activity and growth of MCF-7-E10 cells for each case. We also analyzed relationships b...
Source: Cancer Microenvironment - August 1, 2014 Category: Cancer & Oncology Source Type: research
Clinical Implications of Marker Expression of Carcinoma-Associated Fibroblasts (CAFs) in Patients with Epithelial Ovarian Carcinoma After Treatment with Neoadjuvant Chemotherapy
Abstract
Cancer-associated fibroblasts (CAFs) play an important role in tumor initiation and progression. The aim of this study is to explore the role of 2 CAF markers, fibroblast activated protein (FAP) and α-smooth muscle actin (αSMA), in patients with epithelial ovarian cancer (EOC) post-neoadjuvant chemotherapy. Sixty-six patients with the diagnosis of EOC treated with debulking surgery after neoadjuvant therapy were retrieved from the archives. Immunohistochemistry for FAP and αSMA antibodies were performed on paraffin-embedded tissue. Fisher’s exact test was performed to test the association ...
Source: Cancer Microenvironment - August 1, 2014 Category: Cancer & Oncology Source Type: research
Microenvironmental Influences on Metastasis Suppressor Expression and Function during a Metastatic Cell’s Journey
Abstract
Metastasis is the process of primary tumor cells breaking away and colonizing distant secondary sites. In order for a tumor cell growing in one microenvironment to travel to, and flourish in, a secondary environment, it must survive a series of events termed the metastatic cascade. Before departing the primary tumor, cells acquire genetic and epigenetic changes that endow them with properties not usually associated with related normal differentiated cells. Those cells also induce a subset of bone marrow-derived stem cells to mobilize and establish pre-metastatic niches [1]. Many tumor cells under...
Source: Cancer Microenvironment - June 18, 2014 Category: Cancer & Oncology Source Type: research
The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment
Abstract
Neutrophils are myeloid cells that constitute 50–70 % of all white blood cells in the human circulation. Traditionally, neutrophils are viewed as the first line of defense against infections and as a major component of the inflammatory process. In addition, accumulating evidence suggest that neutrophils may also play a key role in multiple aspects of cancer biology. The possible involvement of neutrophils in cancer prevention and promotion was already suggested more than half a century ago, however, despite being the major component of the immune system, their contribution has often been overs...
Source: Cancer Microenvironment - June 4, 2014 Category: Cancer & Oncology Source Type: research
Role of Stromal-Epithelial Interaction in the Formation and Development of Cancer Cells
Abstract
Identification of gene expression mechanisms began with works on embryonic induction. The same mechanism of cell-cell interactions also contributes to the process of oncogenesis. Damage to epithelial cells’ genetic apparatus turns them into precancerous stem cells that are not yet capable of tumor growth. They can be transformed into cancer stem cells and undergo further progression as a result of epigenetic effects of apocrine secretion by surrounding activated stromal cells (mostly myofibroblasts). These factors may activate the damaged genetic information. On the contrary, the level of mal...
Source: Cancer Microenvironment - December 1, 2013 Category: Cancer & Oncology Source Type: research
Inhibition of the Insulin-Like Growth Factor-1 Receptor Enhances Effects of Simvastatin on Prostate Cancer Cells in Co-Culture with Bone
In conclusion, we suggest that IGF-1 inhibition may be a way to strengthen effects of apoptosis-inducing therapies on PC bone metastases; a possibility that needs to be further tested in pre-clinical models. (Source: Cancer Microenvironment)
Source: Cancer Microenvironment - December 1, 2013 Category: Cancer & Oncology Source Type: research
Cysteine (C)-X-C Receptor 4 Regulates NADPH Oxidase-2 During Oxidative Stress in Prostate Cancer Cells
Abstract
Reactive oxygen species (ROS) are implicated in many human diseases, including cancer. We have previously demonstrated that ROS increased the expression and activity of the chemokine receptor, CXCR4, which enhanced metastatic functions in prostate cancer cells. Studies have also revealed that CXCR4 and its ligand, SDF-1α, promoted ROS accumulation; however the source of ROS was not investigated. Recent evidence suggested that ROS accumulation in prostate cancer cell lines was contributed by the NADPH oxidase (NOX) family of enzymes. Herein, we sought to determine whether the CXCR4/SDF-1α sign...
Source: Cancer Microenvironment - December 1, 2013 Category: Cancer & Oncology Source Type: research
Biological resonance for cancer metastasis, a new hypothesis based on comparisons between primary cancers and metastases
Abstract
Many hypotheses have been proposed to try to explain cancer metastasis. However, they seem to be contradictory and have some limitations. Comparisons of primary tumors and matched metastases provide new insight into metastasis. The results show high concordances and minor differences at multiple scales from organic level to molecular level. The concordances reflect the commonality between primary cancer and metastasis, and also mean that metastatic cancer cells derived from primary cancer are quite conservative in distant sites. The differences reflect variation that cancer cells must acquire n...
Source: Cancer Microenvironment - December 1, 2013 Category: Cancer & Oncology Source Type: research
Paracrine Activation of Chemokine Receptor CCR9 Enhances The Invasiveness of Pancreatic Cancer Cells
Abstract
Chemokine receptors mediate cancer progression and metastasis. We have previously examined chemokine receptor CCR9 expression in pancreatic cancer. Here, our objective was to evaluate pancreatic stellate cells (PSCs) as a source of CCL25, the CCR9 ligand, and as an activator of CCL25-CCR9 signaling in pancreatic cancer cells. CCL25 and CCR9 expression levels in human pancreatic cancer tissues and normal human pancreas were assessed by immunohistochemsitry. In vitro secretion of CCL25 in PSCs and PANC-1 cells was verified by enzyme-linked immunosorbent assay. Pancreatic cancer cell invasion was ...
Source: Cancer Microenvironment - December 1, 2013 Category: Cancer & Oncology Source Type: research
