Interaction between cancer cells and cancer-associated fibroblasts after cisplatin treatment promotes cancer cell regrowth

This study examined whether cancer-associated fibroblasts (CAFs), a major component of a tumor microenvironment, promote cancer cell regrowth after chemotherapy. First, we treated human lung adenocarcinoma cell line A549 and CAFs from four patients with cisplatin. Cisplatin treatment inhibited the viable cell number of A549 cells and induced epithelial –mesenchymal transition. After cisplatin was removed, A549 cells continued to manifest the mesenchymal phenotype and proliferated 2.2-fold in 4 days (regrowth of A549 cells). Cisplatin treatment inhibited the viable cell number of CAFs from four patients also. The CM (derived from cisplatin-pretr eated CAFs from two patients) significantly enhanced the regrowth of cisplatin-pretreated A549 cells, and the CM derived from cisplatin-naïve CAFs marginally enhanced A549 regrowth. By contrast, the CM derived from either cisplatin-pretreated CAFs or cisplatin-naïve CAFs failed to enhance the grow th of cisplatin-naïve A549 cells. The CM derived from cisplatin-pretreated CAFs did not enhance the proliferation of A549 cells in which epithelial–mesenchymal transition was induced by TGFβ-1. Our findings indicate the possibility that humoral factors from cisplatin-pretreated CAFs promote the regrowth of cisplatin-pretreated A549 cells. These results suggest that interactions between cancer cells and CAFs may significantly enhance cancer cell regrowth within the tumor microenvironment after cisplatin tre...
Source: Human Cell - Category: Cytology Source Type: research

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ahipal Biliary tract cancers (BTCs) are a heterogeneous group of adenocarcinomas that originate from the epithelial lining of the biliary tree. BTCs are characterized by presentation with advanced disease precluding curative surgery, rising global incidence, and a poor prognosis. Chemotherapy is the mainstay of the current treatment, which results in a median overall survival of less than one year, underscoring the need for novel therapeutic agents and strategies. Next-generation sequencing-based molecular profiling has shed light on the underpinnings of the complex pathophysiology of BTC and has uncovered numerous act...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Several patient-derived tumor models emerged recently as robust preclinical drug-testing platforms. However, their potential to guide clinical therapy remained unclear. Here, we report a model called patient-derived tumor-like cell clusters (PTCs). PTCs result from the self-assembly and proliferation of primary epithelial, fibroblast, and immune cells, which structurally and functionally recapitulate original tumors. PTCs enabled us to accomplish personalized drug testing within 2 weeks after obtaining the tumor samples. The defined culture conditions and drug concentrations in the PTC model facilitate its clinical applica...
Source: Science Translational Medicine - Category: Biomedical Science Authors: Tags: Research Resources Source Type: research
We report the case of a 50-yr-old woman who was diagnosed with concomitant endometrial adenocarcinoma and uterine leiomyosarcoma. The sarcomatous neoplasm was positive for anti-smooth muscle actin and CD10, and focally positive for Cytokeratin AE1/AE3 and Cytokeratin Cam 5.2. She underwent total abdominal hysterectomy with bilateral salpingoopherectomy followed by radiation, brachytherapy, and chemotherapy. Three years later, she presented with cough and dyspnea and was found to have pulmonary metastasis. These tumor cells were positive for anti-smooth muscle actin, Cytokeratin AE1/AE3, Cytokeratin Cam 5.2, and epithelial ...
Source: International Journal of Gynecological Pathology - Category: Pathology Tags: PATHOLOGY OF THE CORPUS: CASE REPORTS Source Type: research
ConclusionsHerein, the expression profiles, oncogenic roles, regulators and inhibitors of DNMT1 in PDACs are presented and discussed. DNMT1 is overexpressed in PDAC cases compared with non-cancerous pancreatic ducts, and its expression gradually increases from pre-neoplastic lesions to PDACs. DNMT1 plays oncogenic roles in suppressing PDAC cell differentiation and in promoting their proliferation, migration and invasion, as well as in induction of the self-renewal capacity of PDAC cancer stem cells. These effects are achieved via promoter hypermethylation of tumor suppressor genes, including cyclin-dependent kinase inhibit...
Source: Cellular Oncology - Category: Cancer & Oncology Source Type: research
Somatic alterations in the epidermal growth factor receptor gene (EGFR) result in aberrant activation of kinase signaling and occur in ∼15% of non-small cell lung cancers (NSCLC). Patients diagnosed with EGFR-mutant NSCLC have good initial clinical response to EGFR tyrosine kinase inhibitors (EGFR TKIs), yet tumor recurrence is common and quick to develop. Mechanisms of acquired resistance to EGFR TKIs have been studied extensively over the past decade. Great progress has been made in understanding two major routes of therapeutic failure: additional genomic alterations in the EGFR gene and activation of alternative kin...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Johnson Hershberger EGFR tyrosine kinase inhibitors (EGFR TKIs) are the standard of care treatment for patients with EGFR-mutant lung adenocarcinoma (LUAD). Although initially effective, EGFR TKIs are not curative. Disease inevitably relapses due to acquired drug resistance. We hypothesized that vitamin D metabolites could be used with EGFR TKIs to prevent therapeutic failure. To test this idea, we investigated the link between serum 25-hydroxyvitamin D3 (25(OH)D3) and progression-free survival (PFS) in patients with EGFR-mutant LUAD that received EGFR TKIs (erlotinib n = 20 and afatinib n = 1). Patients who were 25...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
RARITAN, NJ, March 10, 2020 – The Janssen Pharmaceutical Companies of Johnson &Johnson announced today that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for JNJ-61186372 (JNJ-6372) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) Exon 20 insertion mutations, whose disease has progressed on or after platinum-based chemotherapy. JNJ-6372 is an EGFR-mesenchymal epithelial transition factor (MET) bispecific antibody that targets activating and resistant EGFR and MET mutations and amplifications.[1]...
Source: Johnson and Johnson - Category: Pharmaceuticals Tags: Innovation Source Type: news
Abstract BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a very lethal disease that can develop therapy resistance over time. The dense stroma in PDAC plays a critical role in tumor progression and resistance. How this stroma interacts with the tumor cells and how this is influenced by chemotherapy remain poorly understood. METHODS: The backbone of this study is the parallel transcriptome analysis of human tumor and mouse stroma in two molecular and clinical representative patient-derived tumor xenografts models. Mice (8 animals per group) were treated for 4 weeks with gemcitabine or control. We studie...
Source: Translational Oncology - Category: Cancer & Oncology Authors: Tags: Transl Oncol Source Type: research
Authors: Darzi S, Mirzaei SA, Elahian F, Shirian S, Peymani A, Rahmani B, Dibazar SP, Aali E Abstract The capability of flavonoids in sensitizing cancer cells was demonstrated in numerous works to chemotherapy and converse multidrug resistance by modulating efflux pumps and apoptosis mechanisms. Three flavonoids, namely, bavachinin, tephrosin, and candidone, have been recently introduced to cancer treatment research presenting various activities, such as antibacterial, immunomodulatory, cell death, and anticancer. Less information exists regarding the therapeutic significance of these flavonoids in cancer treatment...
Source: Evidence-based Complementary and Alternative Medicine - Category: Complementary Medicine Tags: Evid Based Complement Alternat Med Source Type: research
In this study, we firstly demonstrated that MALAT1 expression was up-regulated in the BC tissues compared to the normal adjacent tissues and elevated in the cancer cells compared to the epithelial immortalized cells. Secondly, we found that suppression of MALAT1 enhanced the chemotherapeutic drug sensitivity and inhibited the cisplatin resistance of the BC cells. Thirdly, we showed that MALAT1 affected the cisplatin resistance of the BC cells via regulating the miR-101-3p/VEGF-C pathway. In summary, this study demonstrates that MALAT1, miR-101-3p and VEGF-C form a regulatory axis to affect the chemo-resistance of BC cells ...
Source: Acta Biochimica et Biophysica Sinica - Category: Biochemistry Authors: Tags: Acta Biochim Biophys Sin (Shanghai) Source Type: research
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