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Cancer Biology & Medicine 2022年第1期19卷 30-42页

作者： Wenhui Wang Li Wang Junjun She Jun Zhu Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount SinaiNew YorkNY 10029USA Sema4 a Mount Sinai ventureStamfordCT 06902USA First Affiliate Hospital of Xi’an Jiaotong University Xi’an 710061China Tisch Cancer Institute Icahn School of Medicine at Mount SinaiNew YorkNY 10029USA

Tumor tissues contain both tumor and non-tumor cells,which include infiltrated immune cells and stromal cells,collectively called the tumor microenvironment(TME).Single-cell RNA sequencing(sc RNAseq)enables the examination of heterogeneity of tumor cells and TME.In this review,we examined sc RNAseq datasets for multiple cancer types and evaluated the heterogeneity of major cell type composition in different cancer types.We further showed that endothelial cells and fibroblasts/myofibroblasts in different cancer types can be classified into common subtypes,and the subtype composition is clearly associated with cancer characteristic and therapy response.

关键词： stromal cells tumor microenvironment pan-cancer single-cell RNA sequencing data

Primary stromal cells isolated from human various histological/pathological prostate have different phenotypes and tumor promotion role

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Chinese Medical Journal 2011年第11期124卷 1700-1707页

作者： WANG Xiao-hai ZHAO Fu-jun HAN Bang-rain JIANG Qi WANG Yong-chuan WU Jian-hong TANG Yue-qing ZHANG Yue-ping XIA Shu-jie Department of Urology First People's Hospital Shanghai JiaoTong University Shanghai 200080 China Department of Urology Qilu Hospital Shandong UniversityJinan Shandong 250000 China Department of Urology Affiliated Hospital of Nantong UniversityNantong Jiangsu 226021 China

Background Prostate stromal cells are known to regulate epithelial growth as well as support and maintain epithelial function. However, how stromal cells regulate epithelial cells and what differences among various histological/pathological prostate stromal cells in prostate cancer progression still remain unclear. This study aimed to investigate the different phenotypes of human various histological^pathological prostate stromal cells, and their role in tumor promotion. Methods The different phenotypes of the human normal prostatic peripheral zonal primary stromal cells （NPPF）, transitional zonal primary stromal cells （NPTF）,

关键词： cluster analysis peripheral zone prostate cancer stromal cells

Differences in phenotype and gene expression of prostate stromal cells from patients of varying ages and their influence on tumour formation by prostate epithelial cells

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Asian Journal of Andrology 2011年第5期13卷 732-741页

作者： Yong-Chuan Wang Sheng-Qiang Yu Xiao-Hai Wang Bang-Min Han Fu-Jun Zhao Guang-Hui Zhu Yan Hong Shu-Jie Xia Department of Urology The Affiliated First People＇s Hospital of Shanghai Jiao Tong University School of Medicine Shanghai 200080 China Department of Urology Yantai Yuhuangding Hospital Affiliated with the Medical College of Qingdao University Shandong 264000 China Department of General Surgery The Affiliated First People＇s Hospital of Shanghai Jiao Tong University Shanghai 200080 China

Prostate cancer （PCa） is an age-related disease, and the stromal microenvironment plays an important role in prostatic malignant progression. However, the differences in prostate stromal cells present in young and old tissue are still obscure. We established primary cultured stromal cells from normal prostatic peripheral zone （PZ） of donors of varying ages and found that cultured stromal cells from old donors （PZ-old） were more enlarged and polygonal than those from young donors （PZ-young）. Furthermore, based on immunocytochemical and ultrastructural analysis, the components of stromal cells changed from a majority of fibroblasts to a mixture of fibroblasts and myofibroblasts with increasing donor age. Using a three-dimensional in vitro culture system, we found that PZ-old stromal cells could enhance the proliferation, migration and invasion of cocultured benign BPH-1 and PC-3 cells. Using an in vivo tissue recombination system, we also found that PZ-old stromal cells are more effective than PZ-young cells in promoting tumour formation by BPH-1 cells of high passage（〉100） and PC-3 cells. To probe the possible mechanism of these effects, we performed cDNA microarray analysis and profiled 509 upregulated genes and 188 downregulated genes in PZ-old cells. Among the changed genes, we found genes coding for a subset of paracrine factors that are capable of influencing adjacent epithelial cells; these include hepatocyte growth factor （HGF）, fibroblast growth factor 5 （FGF5）, insulin-like growth factor 2 （IGF2）, insulin-like growth factor-binding protein 4 （IGFBP4）, IGFBP5 and matrix metallopeptidase 1 （MMP1）. Changes in the expression of these genes were further confirmed by quantitative real-time polymerase chain reaction （PCR）, Western blotting and enzyme-linked immunosorbent assays. Overall, our findings indicate that stromal cells from prostate PZ of old donors are more active than similar cells from young donors in promoting the malignant process of adjacent epithelial cells. This finding hints at a new potential

关键词： coculture gene expression peripheral zone phenotype prostate cancer stromal cells

Proliferation and phenotypic changes of stromal cells in response to varying estrogen/androgen levels in castrated rats

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Asian Journal of Andrology 2009年第4期11卷 451-459页

作者： Ying Zhou Xiang-Qian Xiao Lin-Feng Chen Rui Yang Jian-Dang Shi Xiao-Ling Du Helmut Klocker Irwin Park Chung Lee Ju Zhang Department of Biochemistry and Molecular Biology College of Life Sciences Bioactive Materials Key Lab of Ministry of Education Nankai University Tianjin 300071 China Department of Medical Oncology Dana Farber Cancer Institute Harvard Medical School Boston MA 02115 USA Department of Urology Innsbruck Medical University Anichstrasse 35 A-6020 Innsbruck Austria The Department of Urology Northwestern University Feinberg School of Medicine Chicago IL 60611 USA

It is known that human benign prostatic hyperplasia might arise from an estrogen/androgen （E/T） imbalance. We studied the response of castrated rat prostate to different ratios of circulating E/T. The castrated male Wistar rats were randomly injected with E/T at different ratios for 4 weeks. The prostates of E/T （1：100） group showed a distinct prostatic hyperplasia response by prostatic index, hematoxylin and eosin staining, and quantitative immunohistochemical analysis of a-smooth muscle actin （SMA）. In this group, cells positive for Vimentin, non-muscle myosin heavy chain （NMMHC） and proliferating cell nuclear antigen （PCNA） increased in the stroma and epithelium. Furthermore, the mRNA levels of smooth muscle myosin heavy chain （SMMHC） and NMMHC increased. So E/T at a ratio of 1：100 can induce a stromal hyperplastic response in the prostate of castrated rats. The main change observed was an increase of smooth muscle cells, whereas some epithelial changes were also seen in the rat prostates.

关键词： androgens castration estrogen prostatic hyperplasia rat stromal cells

Tumor formation of prostate cancer cells influenced by stromal cells from the transitional or peripheral zones of the normal prostate

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Asian Journal of Andrology 2009年第2期11卷 176-182页

作者： Fu-Jun Zhao Bang-Min Han Sheng-Qiang Yu Shu-Jie Xia Department of Urology Shanghai First People’s HospitalShanghai Jiao Tong UniversityShanghai 200080China

This study was designed to investigate the different involvements of prostatic stromal cells from the normal transitional zone(TZ)or peripheral zone(PZ)in the carcinogenesis of prostate cancer(PCa)epithelial cells(PC-3)in vitro and in vivo co-culture models.Ultra-structures and gene expression profiles of primary cultures of human prostatic stromal cells from the normal TZ or PZ were analyzed by electron microscopy and microarray analysis.In vitro and in vivo co-culture models composed of normal TZ or PZ stromal cells and human PCa PC-3 cells were established.We assessed tumor growth and weight in the in vivo nude mice model.There are morphological and ultra-structural differences in stromal cells from TZ and PZ of the normal prostate.In all,514 differentially expressed genes were selected by microarray analysis;483 genes were more highly expressed in stromal cells from TZ and 31 were more highly expressed in those from PZ.Co-culture with PZ stromal cells and transforming growth factor-β1(TGF-β1)increased the tumor growth of PC-3 cells in vitro and in vivo,as well as Bcl-2 expression.On the other hand,stromal cells of TZ suppressed PC-3 cell tumor growth in the mouse model.We conclude that ultra-structures and gene expression differ between the stromal cells from TZ or PZ of the normal prostate,and stroma-epithelium interactions from TZ or PZ might be responsible for the distinct zonal localization of prostate tumor formation.

关键词： co-culture epithelial cells stromal cells transitional zone peripheral zone prostate cancer

Emerging data supporting stromal cell therapeutic potential in cancer:reprogramming stromal cells of the tumor microenvironment for anti-cancer effects

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Cancer Biology & Medicine 2020年第4期17卷 828-841页

作者： Armel H.Nwabo Kamdje Paul F.Seke Etet Richard Tagne Simo Lorella Vecchio Kiven Erique Lukong Mauro Krampera Department of Biomedical Sciences University of NgaoundereFaculty of ScienceNgaoundere 454Cameroon Department of Physiological Sciences and Biochemistry University of NgaoundereGaroua 454Cameroon Center for Sustai nable Health and Development Garoua 454Cameroon Department of Biochemistry Microbiology&ImmunologyUniversity of SaskatchewanCollege of MedicineSaskatoon SK S7N 5E5Canada Department of Medicine University of VeronaSection of HematologyStem Cell Research LaboratoryVerona 37134Italy

After more than a decade of controversy on the role of stromal cells in the tumor microenvironment,the emerging data shed light on pro-tumorigenic and potential anti-cancer factors,as well as on the roots of the discrepancies.We discuss the pro-tumorigenic effects of stromal cells,considering the effects of tumor drivers like hypoxia and tumor stiffness on these cells,as well as stromal cell-mediated adiposity and immunosuppression in the tumor microenvironment,and cancer initiating cells'cellular senescence and adaptive metabolism.We summarize the emerging data supporting stromal cell therapeutic potential in cancer,discuss the possibility to reprogram stromal cells of the tumor microenvironment for anti-cancer effects,and explore some causes of discrepancies on the roles of stromal cells in cancer in the available literature.

关键词： stromal cells tumorigenic effects anti-cancer effects tumor microenvironment reprogramming

Adipose tissue-derived stromal cells express neuronal phenotypes

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Chinese Medical Journal 2004年第3期117卷 425-429页

作者：杨立业刘相名孙兵惠国桢费俭郭礼和 Department of Neurosurgery First Affiliated Hospital Suzhou University Institute of Biochemistry and Cell Biology Shanghai Institute for Biological Sciences Chinese Academy of Sciences 320 Yueyang Road

Background Adipose tissue-derived stromal cells (ADS Cs) can be greatly expanded in vitro, and induced to differentiate into multiple mesenchymal cell types, including osteogenic, chondrogenic, myogenic, and adipogenic cells. This study was designed to investigate the possibility of ADSCs differentiating into neurons.Methods Adipose tissue from rats was digested with collagenase, and adherent stromal cells were cultured. A medium containing a low concentration of fetal bovine serum was adopted to induce the cells to differentiate. ADSCs were identified by immunocytochemistry, and semi-quantitative RT-PCR was applied to detect mRNA expression of neurofilament 1 (NF1), nestin, and neuron-specific enolase (NSE).Results Nestin-positive cells were found occasionally among ADSCs. ADSCs were found to express NSE mRNA and nestin mRNA, but not NF1 mRNA. ADSCs could differentiate into neuron-like cells in a medium composed of a low concentration of fetal bovine serum, and these differentiated cells displayed complicated neuron-like morphologies.Conclusions The data support the hypothesis that adipose tissue contains stem cells capable of differentiating into neurons. These stem cells can overcome their mesenchymal commitment, and may represent an alternative autologous stem cell source for CNS cell transplantation.

关键词： stromal cells adipose tissue neuron phenotype

Marrow stromal cells administrated intracisternally to rats after traumatic brain injury migrate into the brain and improve neurological function

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Chinese Medical Journal 2004年第10期117卷 1576-1578页

作者：胡德志周良辅朱剑虹 Department of Neurosurgery Huashan HospitalFudan University Shanghai 200040 China

Marrow stromal cells(MSCs) have been reported to transplant into injured brain via intravenous or intraarterial or direct intracerebral administration.1-3 In the present study, we observed that MSCs migrated into the brain, survived and diffeneriated into neural cells after they were injected into the cisterna magna of rats, and that the behavior of the rats after traumatic brain injury (TBI) was improved.

关键词： brain injuries transplantation stromal cells bone marrow Cisterna Magna

Comparative study on seeding methods of human bone marrow stromal cells in bone tissue engineering

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Chinese Medical Journal 2004年第4期117卷 576-580页

作者：齐欣刘建国常颖徐莘香 Department of Orthopedic Surgery Department of Neurology

Background In general the traditional static seeding method has its limitation while the dynamic seeding method reveals its advantages over traditional static method. We compared static and dynamic seeding method for human bone marrow stromal cells (hBMSCs) in bone tissue engineering. Methods DNA assay was used for detecting the maximal initial seeding concentration for static seeding. Dynamic and static seeding methods were compared, when scaffolds were loaded with hBMSCs at this maximal initial cell seeding concentration. Histology and scanning electron microscope (SEM) were examined to evaluate the distribution of cells inside the constructs. Markers encoding osteogenic genes were measured by fluorescent RT-PCR. The protocol for dynamic seeding of hBMSCs was also investigated. Results DNA assay showed that the static maximal initial seeding concentration was lower than that in dynamic seeding. Histology and SEM showed even distribution and spread of cells in the dynamically seeded constructs, while their statically seeded counterparts showed cell aggregation. Fluorescent RT-PCR again showed stronger osteogenic potential of dynamically seeded constructs. Conclusion dynamic seeding of hBMSCs is a promising technique in bone tissue engineering.

关键词： tissue engineering bone regeneration stromal cells bone marrow

Angiogenic Potency of Bone Marrow stromal cells Improved by ex Vivo Hypoxia Prestimulation

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2004年第6期24卷 566-568页

作者：毛晓波曾秋棠王祥曹林生白智峰 Department of Cardiology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China

Summary: To study the angiogenic potency of hypoxia-prestimulated bone marrow stromal cells (BMSCs) when transplanted into acute myocardial infarction models of rats. BMSCs were cultured under hypoxia condition for 24 h. Their expression of VEGF was investigated. The rat acute myocardial infarction models were made by coronary artery ligation and divided into 3 groups at random. In normoxia group, twice-passaged BMSCs were labeled with Bromodeoxyuridine (BrdU) and then implanted into the infarction regions and ischemic border of the recipients in 4 weeks. The rats in hypoxia group were implanted with hypoxia-prestimulated BMSCs. In control group, the model rats received only DMEM medium injection. Six-weeks after AMI, the infarction regions were examined to identify the angiogenesis and the expression of the VEGF. Our results showed that viable cells labeled with BrdU could be identified in the host hearts. The infarction regions in normoxia and hypoxia groups had a greater capillary density and increased VEGF expression than the regions in control group. The capillary density and VEGF expression in hypoxia group were higher than in normoxia group. It is concluded that the enhanced expression of VEGF in BMSCs could be induced by ex vivo hypoxia stimulation. BMSCs implantation promoted the angiogenesis in myocardial infarction tissue via supplying exogenic VEGF. Angiogenic potency of bone marrow stromal cells was improved by ex vivo hypoxia prestimulation though the enhanced VEGF expression.

关键词： stromal cells bone marrow myocardial infarction vascular endothelial growth factor angiogenesis