- Review ARTICLE
- Reviews - Extracellular Matrix News
- Analysis of the interaction of extracellular matrix and phenotype of bladder cancer cells
The authors thank Sarah Boyle for assistance with figure, critical reading of and constructive feedback on this manuscript. Bacac M, Stamenkovic I. Metastatic cancer cell.
Annu Rev Pathol. Microenvironmental regulation of tumor progression and metastasis. Nat Med. Tsai JH, Yang J. Epithelial-mesenchymal plasticity in carcinoma metastasis. Genes Dev. Hematopoiesis: an evolving paradigm for stem cell biology. Cell — Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity. Nature —8. Nassar D, Blanpain C. Cancer stem cells: basic concepts and therapeutic implications.
Batlle E, Clevers H. Cancer stem cells revisited. Inhibition of focal adhesion kinase signaling by integrin alpha6beta1 supports human pluripotent stem cell self-renewal. Stem Cells — BMC Cell Biol. Integrins alpha2beta1 and alpha11beta1 regulate the survival of mesenchymal stem cells on collagen I. Cell Death Dis. The cancer stem cell niche: how essential is the niche in regulating stemness of tumor cells?
Cell Stem Cell — Kumar S, Weaver VM.
Mechanics, malignancy, and metastasis: the force journey of a tumor cell. Cancer Metastasis Rev. Biomechanical and biochemical remodeling of stromal extracellular matrix in cancer. Trends Biotechnol. Targeting ECM disrupts cancer progression. Front Oncol. Critical role for lysyl oxidase in mesenchymal stem cell-driven breast cancer malignancy. Singleton PA. Hyaluronan regulation of endothelial barrier function in cancer. Adv Cancer Res. Cancer microenvironment and inflammation: role of hyaluronan. Front Immunol. Dynamic imaging of cancer growth and invasion: a modified skin-fold chamber model.
Histochem Cell Biol. Dynamic interplay between the collagen scaffold and tumor evolution. Curr Opin Cell Biol. Actomyosin-mediated cellular tension drives increased tissue stiffness and beta-catenin activation to induce epidermal hyperplasia and tumor growth. Cancer Cell — Guo W, Giancotti FG. Integrin signalling during tumour progression. Nat Rev Mol Cell Biol. Bainbridge P. Wound healing and the role of fibroblasts. J Wound Care —8, — A negative regulatory mechanism involving 14—zeta limits signaling downstream of ROCK to regulate tissue stiffness in epidermal homeostasis.
Dev Cell — Role of the ECM in notochord formation, function and disease. J Cell Sci. Collagen 18 and agrin are secreted by neural crest cells to remodel their microenvironment and regulate their migration during enteric nervous system development. Development Phenotypic and functional heterogeneity of cancer-associated fibroblast within the tumor microenvironment. Adv Drug Deliv Rev. Kalluri R. The biology and function of fibroblasts in cancer. Nat Rev Cancer — Dvorak HF.
Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. Coussens LM, Werb Z. Inflammation and cancer. Nature —7. Augsten M.
Cancer-associated fibroblasts as another polarized cell type of the tumor microenvironment. Cancer-associated fibroblasts induce epithelial-mesenchymal transition of breast cancer cells through paracrine TGF-beta signalling. Br J Cancer — Carbonic anhydrase IX from cancer-associated fibroblasts drives epithelial-mesenchymal transition in prostate carcinoma cells. Cell Cycle — Reciprocal activation of prostate cancer cells and cancer-associated fibroblasts stimulates epithelial-mesenchymal transition and cancer stemness.
- An American Tourist in London (Travels with Denise Book 1).
- Songs of Honesty & Emotion - A Body of Poetry Exorcised - Vol. 5 Humorous Verse?
- Cell to extracellular matrix interactions and their reciprocal nature in cancer. - Semantic Scholar.
- CODE BLOOD.
Cancer Res. Extracellular matrix: a dynamic microenvironment for stem cell niche. Biochim Biophys Acta — Intestinal stem cell Niche: the extracellular matrix and cellular components. Stem Cells Int Interactions between cancer stem cells and their niche govern metastatic colonization. Nature —U Targeting stromal remodeling and cancer stem cell plasticity overcomes chemoresistance in triple negative breast cancer. Nat Commun. Loss of the Timp gene family is sufficient for the acquisition of the CAF-like cell state.
Nat Cell Biol.
- A Bald Chimpanzee, an Adventure in ABCs?
- Cell-Extracellular Matrix Interactions in Cancer?
- Reviews - Extracellular Matrix News.
Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Cancer-associated fibroblasts regulate the plasticity of lung cancer stemness via paracrine signalling. Mechanoreciprocity in cell migration. Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts. Macrophage diversity enhances tumor progression and metastasis. Macrophage biology in development, homeostasis and disease. Nature — Pollard JW. Trophic macrophages in development and disease.
Nat Rev Immunol. Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest — Transcriptome-based network analysis reveals a spectrum model of human macrophage activation. Immunity — Aras S, Zaidi MR. TAMeless traitors: macrophages in cancer progression and metastasis. A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Expression of Tie-2 by human monocytes and their responses to angiopoietin J Immunol.
CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature —5. Promotion of tumor invasion by tumor-associated macrophages: the role of CSFactivated phosphatidylinositol 3 kinase and Src family kinase motility signaling. Cancers Basel 9:E Mol Cancer Macrophages promote fibroblast growth factor receptor-driven tumor cell migration and invasion in a CXCR2-dependent manner. Mol Cancer Res. Macrophages promote matrix protrusive and invasive function of breast cancer cells via MIP-1 beta dependent upregulation of MYO3A gene in breast cancer cells. Oncoimmunology 5. Tumor-associated macrophages press the angiogenic switch in breast cancer.
Vascular endothelial growth factor-induced skin carcinogenesis depends on recruitment and alternative activation of macrophages. J Pathol. Intratumoral macrophages contribute to epithelial-mesenchymal transition in solid tumors. BMC Cancer Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. Tumor-associated macrophages as incessant builders and destroyers of the cancer stroma. Cancers Basel — Tumor macrophages are pivotal constructors of tumor collagenous matrix. J Exp Med. Condeelis J, Pollard JW. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis.
Cell —6. EMBO J. Lab Invest. A positive feedback loop between mesenchymal-like cancer cells and macrophages is essential to breast cancer metastasis. Cancer stem cells and tumor-associated macrophages: a roadmap for multitargeting strategies. Oncogene — Tumor-associated macrophages promote cancer stem cell-like properties via transforming growth factor-beta1-induced epithelial-mesenchymal transition in hepatocellular carcinoma. Cancer Lett. Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Neutrophils in cancer: neutral no more.
The multifaceted effects of granulocyte colony-stimulating factor in immunomodulation and potential roles in intestinal immune homeostasis. Neutrophil elastase-mediated degradation of IRS-1 accelerates lung tumor growth. Promoting effect of neutrophils on lung tumorigenesis is mediated by CXCR2 and neutrophil elastase.
Reviews - Extracellular Matrix News
Tissue-infiltrating neutrophils constitute the major in vivo source of angiogenesis-inducing MMP-9 in the tumor microenvironment. Neoplasia — Mice deficient in tumor necrosis factor-alpha are resistant to skin carcinogenesis. Overexpression of CXCL5 mediates neutrophil infiltration and indicates poor prognosis for hepatocellular carcinoma. Hepatology — MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Tumor-recruited neutrophils and neutrophil TIMP-free MMP-9 regulate coordinately the levels of tumor angiogenesis and efficiency of malignant cell intravasation.
Am J Pathol. Epithelial-to-mesenchymal transition in pancreatic ductal adenocarcinoma and pancreatic tumor cell lines: the role of neutrophils and neutrophil-derived elastase. Clin Dev Immunol. Freisinger CM, Huttenlocher A. Live imaging and gene expression analysis in zebrafish identifies a link between neutrophils and epithelial to mesenchymal transition.
Inhibition of CXCR2 profoundly suppresses inflammation-driven and spontaneous tumorigenesis. J Clin Invest. Neutrophil-mediated experimental metastasis is enhanced by VEGFR inhibition in a zebrafish xenograft model. Neutrophils increase oral squamous cell carcinoma invasion through an invadopodia-dependent pathway. Cancer Immunol Res. Neutrophils drive accelerated tumor progression in the collagen-dense mammary tumor microenvironment. Breast Cancer Res. Neutrophil extracellular traps in cancer progression.
Cell Mol Life Sci. Erpenbeck L, Schon MP. Neutrophil extracellular traps: protagonists of cancer progression? Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis. Integrin-dependent cell adhesion to neutrophil extracellular traps through engagement of fibronectin in neutrophil-like cells. Thematic review series: adipocyte biology. Adipose tissue function and plasticity orchestrate nutritional adaptation. J Lipid Res. Adipose tissue and adipocytes support tumorigenesis and metastasis. The fat and the bad: Mature adipocytes, key actors in tumor progression and resistance.
Oncotarget — Identification of white adipocyte progenitor cells in vivo. Cell —9. Adipogenesis: from stem cell to adipocyte. Annu Rev Biochem. Stem Cells —8. Hematopoietic stem cell origin of adipocytes. Exp Hematol. Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Adipocyte-derived fibroblasts promote tumor progression and contribute to the desmoplastic reaction in breast cancer.
Analysis of the interaction of extracellular matrix and phenotype of bladder cancer cells
Mature breast adipocytes promote breast cancer cell motility. Exp Mol Pathol. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Obesity and cancer—mechanisms underlying tumour progression and recurrence. Nat Rev Endocrinol. Emerging concepts linking obesity with the hallmarks of cancer. Trends Endocrinol Metab. Obesity-induced inflammation and desmoplasia promote pancreatic cancer progression and resistance to chemotherapy. Cancer Discov. Obesity-dependent changes in interstitial ECM mechanics promote breast tumorigenesis.
Sci Transl Med. Tumor cell-educated periprostatic adipose tissue acquires an aggressive cancer-promoting secretory profile. Cell Physiol Biochem. Park J, Scherer PE. Adipocyte-derived endotrophin promotes malignant tumor progression. Human renal adipose tissue induces the invasion and progression of renal cell carcinoma. Paradoxical roles of the immune system during cancer development. Sasada T, Suekane S.
Variation of tumor-infiltrating lymphocytes in human cancers: controversy on clinical significance. Immunotherapy — Tumor-infiltrating ILproducing gammadelta T cells support the progression of tumor by promoting angiogenesis. Eur J Immunol. ILproducing gammadelta T cells and neutrophils conspire to promote breast cancer metastasis. Genes were not weighted by expression levels, and biological networks were built on this assumption.
One strategy for analyzing the significance of gene clusters identified by correlational clustering is based upon the assumption that co-expressed genes are likely to share common regulatory motifs [ 21 ]. The results depend upon the reference chosen thereby reflecting Bayesian probability. If the entire genome is selected as the reference, the results will emphasize TREs common to bladder cells and would therefore identify tissue-specific TREs.
Alternately, if the list of all genes expressed on a given matrix is selected as the reference, then the results should be enriched in those TREs responsible for the clustering rather than tissue-specific promoters. If the reference is the list of hypervariable genes, then significance of the partitioning of the hypervariable genes by clusters and TREs is identified. The PAINT analysis was performed against each of the indicated references, but only the reference against all hypervariable genes was reported.
Venn diagram of hypervariable genes expressed on different matrixes. The size of circles does not represent relative number of genes in each group. X-ray repair complementing defective repair in Chinese hamster cells 5 double-strand-break rejoining; Ku autoantigen, 80 kDa.
Hierarchical clustering of hypervariable genes across different cell lines on different matrixes. Hierarchical clustering of genes up- red color or downregulated green color on the given 6 cell lines. Colored bars outline individual clusters used for subsequent analysis. Driving signatures and ontologies of gene clusters on different matrixes. Driving signature. Top Functions. Contained in the 33 genes that were hypervariable on both ECM preparations but not on plastic were two networks of 15 and 11 genes respectively.
The 11 gene network consisted of a c-Myc response network and EGF signaling. These genes are also listed in Table 4 and the pathways are presented [see Additional file 6 ]. Filtered maps of TREs on gene clusters of hypervariable genes identified in cells growing on different matrixes. Colored bars represent individual gene clusters. In this study we sought to identify genes that modulate the malignant phenotype of bladder cancer. The experimental design made genes modulating the phenotype hypervariable as six different cell lines with different inherent malignancies were grown on plastic and two different extracellular matrices.
Because varying the substrate on which the cells are grown changes the malignant phenotype, genes that modulate the phenotype were therefore brought to the fore. Our approach for analysis of this noisy dataset first consisted of identifying the subset of hypervariable genes because this subset will contain the set of genes encapsulating the relevant biological effect [ 14 ]. This step is designed to minimize false negatives for further in silico analysis.
The subsequent steps sought to generate testable hypotheses with minimal false positives. By finding gene ontologies, pathways and TRE motifs that were significantly enriched within individual clusters, genes that potentially functioned together in pathways were identified. Because microarray studies are weighted toward high expression genes, these approaches, particularly pathways and TRE analysis can identify effects due to low expression genes such as transcription factors whose expression may be too low to be detected with the microarray.
Because these determinations are made with reference to statistical probability, the only step in the analysis process that does not contain a quantitative estimate of statistical significance is the clustering. Except for clusters M4 and P7 the driving force for clustering appeared to represent the behavior of individual cell lines rather than overall malignancy. However, these two clusters identify genes generally expressed at higher levels in the malignant cells than in the HUC cells.
Of particular interest is the apparent activation of pro-survival AKT1 signaling in the malignant cells on Matrigel [see Additional file 6 ]. Other ontologies in these two clusters clearly showed connections to cancer and apoptosis. While the mechanisms identified as operating only within a single cell line are probably less interesting than those operating in several, identification of a range of behaviors in bladder cancers could become useful if pathway-specific drugs are developed.
Some 20 genes were identified as being hypervariable, regardless the substrate. These represent a group of genes that are not modulated by the ECM but are differentially expressed among the different cell lines. Examples include Prohibitin PHB , a survival gene, which is entirely matrix-independent. The connection with AKT1 survival pathway is clear. AKT1 can cause resistance to therapy in other cancers [ 25 ]. Interestingly, genes coding for two polysaccharide-binding proteins were also present. That these two would be differentially expressed by different cell types growing on polysaccharide-containing gels and the minimal endogenous matrix secreted by cells growing on plastic is consistent with the role of these molecules in differentiation and growth [ 26 ].
Additionally, 33 genes were identified as being hypervariable on both Matrigel and SISgel, in spite of the suppression of many features of the malignant phenotype on the latter. These genes probably represent a "core" set of cancer genes. Ontologies for this cluster of genes were cancer, cell morphology and cell cycle networks. Eleven of these 33 genes are interconnected within the MYC network.
Deregulation of MYC genes is associated with several malignancies [ 29 ]. Although the ECM can have major effects on the biology of individual cancers, a core of oncogenes involved in the p53 and MYC networks is unaffected. Interestingly, a set of signature genes for the suppression of the malignant phenotype by SISgel was not observed.
Either the correct probes are not on the array, or each cell type respond uniquely to a changing matrix. Previous results showed this response was not due to integrin signaling [ 9 ] as has been reported by Weaver, et. The TRE analysis confirmed the uniqueness of the clustering and suggests that a limited set of TREs may be driving gene expression in this study. Notable is Hand1, which appears in most of the genes. This gene has been identified as playing a role in heart development [ 31 ], but the abundance in these genes that are expressed in bladder suggests it may also act as a bladder-specific factor.
The corresponding transcription factor has been shown to promote cell growth in common human carcinomas [ 32 ] and to be dependent on the p53 pathway [ 32 , 33 ] supporting its role in upregulating the cluster in cancer cells. This combination suggests loss of epithelial differentiation. Bladder cancer cells were earlier demonstrated to contain both functional androgen and estrogen receptors without regard to the sex of the donor [ 34 , 35 ] while myogenin was primary expressed in rhabdomyosarcomas [ 36 , 37 ]. Identification of myogenin expression in bladder cancer cell lines is novel, and further research will be needed to determine if this transcription factor is actually active.
Comparisons to other microarray studies are, in general, less informative because of wide differences among array technologies [ 38 ] and criteria to identify "significant" genes. Nonetheless the composition of Cluster M4, which is comprised of genes that are under-expressed in HUC cells in comparison to all the cancer cells, shows 3 of the 28 genes in the cluster corresponded to 3 of the 29 genes identified as being diagnostic for TCC in patient samples [ 39 ]. This association suggests this cluster might provide additional diagnostic genes which is strongly supported by the finding of the presponsive gene network.
In addition, although the comparison was made difficult by a lack of accession numbers or universal gene symbols, considerable correspondence between the 32 genes identified as hypervariable in 3-dimensional growth was noted with the set of genes reported to differentially expressed between superficial and invasive TCC [ 40 ].
Activation of the AKT1 survival pathway on Matrigel suggests this pathway could be relevant to clinical bladder cancer. The p53 response network is confirmed to play a central role, as does c-MYC signaling. Free Preview. Will discuss how integrins and extracellular matrix components control cancer initiation, progression and metastasis. Buy eBook. Buy Hardcover. Buy Softcover. FAQ Policy. About this book Cells require interactions with extracellular matrix ECM components in order to undergo normal morphogenesis with respect to organogenesis.