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Breast cancer associated fibroblasts Promote MCF-7 Invasion in vitro by Secretion of HGF

Journal of Huazhong University of Science and Technology(Medical Sciences) 2012年第1期32卷 92-96页

作者：陈平波墨青青王蓓蓓翁丹卉吴鹏陈刚 Department of Obstetrics and Gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology

This study was aimed to explore the influence of breast cancer associated fibroblasts (CAFs) in migration and invasion of breast cancer cell line MCF-7,and investigate whether hepatocyte growth factor (HGF) is involved in this *** breast CAFs and their corresponding normal breast fi-broblasts (NFs) were obtained by collagenase *** the basis of the co-culture,the migration and invasion capacity of MCF-7 cells was compared between CAFs and NFs by *** differ-ence in the HGF expression between them was detected by *** secretion of HGF was knocked down by using RNA interference technology in *** the changes of migration and invasion ca-pacity of MCF-7 cells were investigated by ***,we isolated high-purity CAFs and NFs,and the CAFs had a stronger ability in promoting MCF-7 migration and invasion than the *** results demonstrated that CAFs secreted higher HGF,and the capacity of MCF-7 migration and invasion was declined after knocking down the secretion of HGF in CAFs by RNA *** is suggested that CAFs can promote MCF-7 migration and invasion through HGF in vitro.

关键词： cancer associated fibroblasts breast cancer hepatocyte growth factor invasion

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Tumor–stromal cross-talk modulating the therapeutic response in pancreatic cancer

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Hepatobiliary & Pancreatic Diseases International 2018年第5期17卷 461-472页

作者： Christopher C.M.Neumann Ellen von Horschelmann Anja Reutzel-Selke Elisabeth Seidel Igor Maximilian Sauer Johann Pratschke Marcus Bahra Rosa Bianca Schmuck Department of Surgery Campus Charité Mitte Campus Virchow-KlinikumExperimental SurgeryCharité-Universitatsmedizin BerlinBerlinGermany Berlin Institute of Health Department of SurgeryCampus CharitéMitte and Campus Virchow-KlinikumAugustenburger Platz 113353 BerlinGermany

Background: Pancreatic ductal adenocarcinoma(PDAC) is a highly malignant solid tumor with a dismal prognosis. The stroma component makes up to 90% of the tumor mass and is thought to be one of the main reasons for the tumor’s high chemoresistance. cancer associated fibroblasts(CAFs) have previously been identified to be the key stromal players. This is the first time we provide detailed in vitro experiments investigating tumor–stromal interactions when exposed to three well-known chemotherapeutic agents. Methods: Monocultures, indirect and direct co-cultures of two PDAC cell lines(AsPC and Panc-1) and six primary patients derived CAFs were treated with gemcitabine, nab-paclitaxel and the γ-secretaseinhibitor(GSI) DAPT. The cell viability of each component was measured with XTT. Finally, IL-6 concentrations of the supernatants were analyzed. Results: On the contrary to PDAC cell lines, CAF monocultures hardly responded to any treatment which suggested that stroma(CAFs) itself is more resistant to standard chemo-treatments than the epithelial cancer cells. Moreover, only a weak chemotherapeutic response was observed in direct co-cultures of cancer cells with CAFs. A change in the morphology of direct co-cultures was accompanied with the chemoresistance. CAFs were observed to build cage-like structures around agglomerates of tumor cells. High levels of IL-6 were also associated with a reduced response to therapy. Indirect co-cultures make the tumor–stromal interaction more complex. Conclusions: CAFs are highly chemoresistant. Direct cell–cell contact and high levels of IL-6 correlate with a high chemoresistance.

关键词： Pancreatic cancer Tumor microenvironment cancer associated fibroblasts cancer–stroma co-culture Atroma targeted therapy

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Microenvironment in the pathogenesis of gastric cancer metastasis

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Journal of cancer Metastasis and Treatment 2018年第1期4卷 118-132页

作者： Hiroshi Sawayama Takatsugu Ishimoto Hideo Baba Department of Gastroenterological Surgery Graduate School of Medical SciencesKumamoto UniversityKumamoto 860-8556Japan

Tumor tissues contain cancer cells,other cellular and non-cellular comp onen *** microe nvir onments consist of cancer cells and various types of stromal cells,can cer associated fibroblasts,bone marrow-derived cells,en dothelial cells,and hematopoietic cells,mainly tumor-associated macrophages and tumor-infiltrating *** recent evidence has demonstrated that alteration of tumor microenvironments is deeply implicated in tumor progression and metastasis in gastric can cer(GC)*** in vestigati ons have provided in sights into the molecular mecha ni sms of the interaction between tumor cells and tumor *** between cancer cells and their microe nvir onment with cytok ines and microRNA in extracellular vesicles,such as the exosome,can have a substa ntial impact on tumor *** ons in the tumor microe nvironment may play a crucial role in facilitating the progression of tumor cells and metastasis,as well as the activation of cell signaling pathways,which are associated with GC cell proliferati on and in vasi on by genetic or epigenetic *** this review,significant molecular in sights into the tumor microenvironment,which consist of cancer associated fibroblasts,bone marrow-derived cells,tumor-associated macrophages and tumor-infiltrating lymphocytes;the interactions between cancer cells and their microenvironment;and the clinical impacts of alterations of GC microenvironments will be discussed.

关键词： Tumor microenvironments cancer associated fibroblasts bone marrow-derived cells tumor-associated macrophages tumor-infiltrating lymphocytes

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New Path to Treating Pancreatic cancer: TRAIL Gene Delivery Targeting the Fibroblast-enriched Tumor Microenvironment

New Path to Treating Pancreatic Cancer: TRAIL Gene Delivery ...

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2018年第十二届中国药物制剂大会

作者： Haiping Jiang Sujuan Wang Xuefei Zhou 刘祥瑞 Youqing Shen Key Laboratory of Biomass Chemical Engineering of Ministry of Education and Center for Bionanoengineering College of Chemical and Biological Engineering Zhejiang University

Gene therapy has shown promise in antitumor strategies for advanced cancer. However, efficient and safe delivery of potent therapeutic gene expressing in specific tumor tissues remains elusive, especially when there exist stromal obstacles. Here we report a non-viral gene delivery approach targeting pancreatic stellate cells（PSCs） as the transfection host in the fibroblast-enriched tumor microenvironment of pancreatic cancer. Plasmid DNA（pDNA） encapsulated in branched polyethylenemine（BPEI） was found to selectively transfect PSCs rather than pancreatic cancer cells and other fibroblast cell lines. Mechanism investigations reveal that the highly expressed fibroblast growth factor receptors（FGFRs） in PSCs facilitated the cellular uptake of polyplexes in PSCs. This delivery platform carrying gene encoding of TNF-related apoptosis-inducing ligand（TRAIL） displayed effective by-stander effect and tumor cell-selective cytotoxicity. More importantly, the therapeutic efficacy was proved in a PSC-enriched orthotopic pancreatic tumor model. Thus, this gene delivery strategy smartly converts PSCs as the microenvironment obstacle for drug delivery into the producer and reservoir of selective tumor-killing proteins.

关键词： pancreatic cancer cancer associated fibroblasts gene delivery TRAIL pancreatic stellate cells

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