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Pericytes in Metastasis

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Pericyte Biology in Disease

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1147))

Abstract

Pericytes have long been known to contribute indirectly to tumour growth by regulating angiogenesis. Thus, remodelling tumour blood vessels to maintain blood supply is critical for continued tumour growth. A role for pericytes in restricting leakage of tumour cells through blood vessels has also become evident given that adequate pericyte coverage of these blood vessels is critical for maintaining vascular permeability. Interestingly, the relocation of pericytes from blood vessels to the tumour microenvironment results in the emergence of different properties in these cells that actively promote tumour growth and metastasis—functions not associated with their well-studied role in vascular stability and permeability. These form the focus of this review.

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References

  • Bergers, G., et al. (2003). Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. The Journal of Clinical Investigation, 111(9), 1287–1295.

    Article  CAS  Google Scholar 

  • Birbrair, A., & Frenette, P. S. (2016). Niche heterogeneity in the bone marrow. Annals of the New York Academy of Sciences, 1370(1), 82–96.

    Article  Google Scholar 

  • Calon, A., et al. (2015). Stromal gene expression defines poor-prognosis subtypes in colorectal cancer. Nature Genetics, 47(4), 320–329.

    Article  CAS  Google Scholar 

  • Caplan, A. I. (2008). All MSCs are pericytes? Cell Stem Cell, 3(3), 229–230.

    Article  CAS  Google Scholar 

  • Cirri, P., & Chiarugi, P. (2011). Cancer associated fibroblasts: the dark side of the coin. American Journal of Cancer Research, 1(4), 482–497.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cooke, V. G., et al. (2012). Pericyte depletion results in hypoxia-associated epithelial-to-mesenchymal transition and metastasis mediated by met signaling pathway. Cancer Cell, 21(1), 66–81.

    Article  CAS  Google Scholar 

  • Crisan, M., et al. (2008). A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell, 3(3), 301–313.

    Article  CAS  Google Scholar 

  • Cunha, G. R., et al. (2003). Role of the stromal microenvironment in carcinogenesis of the prostate. International Journal of Cancer, 107(1), 1–10.

    Article  CAS  Google Scholar 

  • Druker, B. J. (2002). STI571 (Gleevec) as a paradigm for cancer therapy. Trends in Molecular Medicine, 8(4 Suppl), S14–S18.

    Article  CAS  Google Scholar 

  • Dulauroy, S., et al. (2012). Lineage tracing and genetic ablation of ADAM12(+) perivascular cells identify a major source of profibrotic cells during acute tissue injury. Nature Medicine, 18(8), 1262–1270.

    Article  CAS  Google Scholar 

  • Erber, R., et al. (2004). Combined inhibition of VEGF and PDGF signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms. The FASEB Journal, 18(2), 338–340.

    Article  CAS  Google Scholar 

  • Finak, G., et al. (2008). Stromal gene expression predicts clinical outcome in breast cancer. Nature Medicine, 14(5), 518–527.

    Article  CAS  Google Scholar 

  • Frame, M. C., & Serrels, A. (2015). FAK to the rescue: activated stroma promotes a “safe haven” for BRAF-mutant melanoma cells by inducing FAK signaling. Cancer Cell, 27(4), 429–431.

    Article  CAS  Google Scholar 

  • Fujita, H., et al. (2010). alpha-Smooth muscle actin expressing stroma promotes an aggressive tumor biology in pancreatic ductal adenocarcinoma. Pancreas, 39, 1254–1262.

    Article  CAS  Google Scholar 

  • Greenhalgh, S. N., Conroy, K. P., & Henderson, N. C. (2015). Healing scars: targeting pericytes to treat fibrosis. QJM: An International Journal of Medicine, 108(1), 3–7.

    Article  CAS  Google Scholar 

  • Hamzah, J., et al. (2008). Vascular normalization in Rgs5-deficient tumours promotes immune destruction. Nature, 453(7193), 410–414.

    Article  CAS  Google Scholar 

  • Hosaka, K., et al. (2013). Tumour PDGF-BB expression levels determine dual effects of anti-PDGF drugs on vascular remodelling and metastasis. Nature Communications, 4, 2129.

    Article  Google Scholar 

  • Huang, J., et al. (2018). Adipocyte p62/SQSTM1 suppresses tumorigenesis through opposite regulations of metabolism in adipose tissue and tumor. Cancer Cell, 33(4), 770–784 e6.

    Article  CAS  Google Scholar 

  • Hung, S. C., et al. (2005). Mesenchymal stem cell targeting of microscopic tumors and tumor stroma development monitored by noninvasive in vivo positron emission tomography imaging. Clinical Cancer Research, 11(21), 7749–7756.

    Article  CAS  Google Scholar 

  • Kalluri, R., & Zeisberg, M. (2006). Fibroblasts in cancer. Nature Reviews. Cancer, 6(5), 392–401.

    Article  CAS  Google Scholar 

  • Karnoub, A. E., et al. (2007). Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature, 449(7162), 557–563.

    Article  CAS  Google Scholar 

  • Kawase, E., et al. (2004). Gbb/Bmp signaling is essential for maintaining germline stem cells and for repressing bam transcription in the Drosophila testis. Development, 131(6), 1365–1375.

    Article  CAS  Google Scholar 

  • Kramann, R., & Humphreys, B. D. (2014). Kidney pericytes: Roles in regeneration and fibrosis. Seminars in Nephrology, 34(4), 374–383.

    Article  CAS  Google Scholar 

  • Kuhnert, F., et al. (2008). Soluble receptor-mediated selective inhibition of VEGFR and PDGFRbeta signaling during physiologic and tumor angiogenesis. Proceedings of the National Academy of Sciences of the United States of America, 105(29), 10185–10190.

    Article  CAS  Google Scholar 

  • Lin, S.-L., et al. (2008). Pericytes and perivascular fibroblasts are the primary source of collagen-producing cells in obstructive fibrosis of the kidney. The American Journal of Pathology, 173(6), 1617–1627.

    Article  CAS  Google Scholar 

  • Lindblom, P., et al. (2003). Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall. Genes & Development, 17(15), 1835–1840.

    Article  CAS  Google Scholar 

  • Maciag, P. C., et al. (2008). Cancer immunotherapy targeting the high molecular weight melanoma-associated antigen protein results in a broad antitumor response and reduction of pericytes in the tumor vasculature. Cancer Research, 68(19), 8066–8075.

    Article  CAS  Google Scholar 

  • McLean, K., et al. (2011). Human ovarian carcinoma-associated mesenchymal stem cells regulate cancer stem cells and tumorigenesis via altered BMP production. The Journal of Clinical Investigation, 121(8), 3206–3219.

    Article  CAS  Google Scholar 

  • Mederacke, I., et al. (2013). Fate-tracing reveals hepatic stellate cells as dominant contributors to liver fibrosis independent of its etiology. Nature Communications, 4, 2823–2823.

    Article  Google Scholar 

  • Mills, S. J., et al. (2015). Effects of human pericytes in a murine excision model of wound healing. Experimental Dermatology, 24(11), 881–882.

    Article  Google Scholar 

  • Mishra, P. J., et al. (2008). Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells. Cancer Research, 68(11), 4331–4339.

    Article  CAS  Google Scholar 

  • Morikawa, S., et al. (2002). Abnormalities in pericytes on blood vessels and endothelial sprouts in tumors. The American Journal of Pathology, 160(3), 985–1000.

    Article  Google Scholar 

  • Morrison, S. J., & Scadden, D. T. (2014). The bone marrow niche for haematopoietic stem cells. Nature, 505(7483), 327–334.

    Article  CAS  Google Scholar 

  • Navarro, R., et al. (2016). Immune regulation by pericytes: Modulating innate and adaptive immunity. Frontiers in Immunology, 7, 480.

    Article  Google Scholar 

  • Ning, X., et al. (2018). Exosomes released by gastric cancer cells induce transition of pericytes into cancer-associated fibroblasts. Medical Science Monitor, 24, 2350–2359.

    Article  Google Scholar 

  • Nisancioglu, M. H., Betsholtz, C., & Genove, G. (2010). The absence of pericytes does not increase the sensitivity of tumor vasculature to vascular endothelial growth factor-A blockade. Cancer Research, 70(12), 5109–5115.

    Article  CAS  Google Scholar 

  • Olumi, A. F., et al. (1999). Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Research, 59(19), 5002–5011.

    CAS  PubMed  Google Scholar 

  • Paiva, A. E., et al. (2018). Pericytes in the premetastatic niche. Cancer Research, 78(11), 2779–2786.

    Article  CAS  Google Scholar 

  • Paquet-Fifield, S., et al. (2009). A role for pericytes as microenvironmental regulators of human skin tissue regeneration. The Journal of Clinical Investigation, 119(9), 2795–2806.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pietras, K., & Ostman, A. (2010). Hallmarks of cancer: interactions with the tumor stroma. Experimental Cell Research, 316(8), 1324–1331.

    Article  CAS  Google Scholar 

  • Quante, M., et al. (2011). Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth. Cancer Cell, 19(2), 257–272.

    Article  CAS  Google Scholar 

  • Ribeiro, A. L., & Okamoto, O. K. (2015). Combined effects of pericytes in the tumor microenvironment. Stem Cells International, 2015, 868475.

    Article  Google Scholar 

  • Ruoslahti, E. (2002). Specialization of tumour vasculature. Nature Reviews. Cancer, 2(2), 83–90.

    Article  Google Scholar 

  • Sa da Bandeira, D., Casamitjana, J., & Crisan, M. (2017). Pericytes, integral components of adult hematopoietic stem cell niches. Pharmacology & Therapeutics, 171, 104–113.

    Article  CAS  Google Scholar 

  • Sacchetti, B., et al. (2007). Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell, 131(2), 324–336.

    Article  CAS  Google Scholar 

  • Scharpfenecker, M., et al. (2005). The Tie-2 ligand angiopoietin-2 destabilizes quiescent endothelium through an internal autocrine loop mechanism. Journal of Cell Science, 118(Pt 4), 771–780.

    Article  CAS  Google Scholar 

  • Sena, I. F. G., et al. (2018). Glioblastoma-activated pericytes support tumor growth via immunosuppression. Cancer Medicine, 7(4), 1232–1239.

    Article  Google Scholar 

  • Sennino, B., et al. (2007). Sequential loss of tumor vessel pericytes and endothelial cells after inhibition of platelet-derived growth factor B by selective aptamer AX102. Cancer Research, 67(15), 7358–7367.

    Article  CAS  Google Scholar 

  • Shi, Y., et al. (2018). Immunoregulatory mechanisms of mesenchymal stem and stromal cells in inflammatory diseases. Nature Reviews Nephrology, 14, 493–507.

    Article  CAS  Google Scholar 

  • Sinha, D., et al. (2016). Pericytes promote malignant ovarian cancer progression in mice and predict poor prognosis in serous ovarian cancer patients. Clinical Cancer Research, 22(7), 1813–1824.

    Article  CAS  Google Scholar 

  • Song, X., et al. (2004). Bmp signals from niche cells directly repress transcription of a differentiation-promoting gene, bag of marbles, in germline stem cells in the Drosophila ovary. Development, 131(6), 1353–1364.

    Article  CAS  Google Scholar 

  • Stapor, P. C., et al. (2014). Pericyte dynamics during angiogenesis: new insights from new identities. Journal of Vascular Research, 51(3), 163–174.

    Article  Google Scholar 

  • Studeny, M., et al. (2002). Bone marrow-derived mesenchymal stem cells as vehicles for interferon-beta delivery into tumors. Cancer Research, 62(13), 3603–3608.

    CAS  PubMed  Google Scholar 

  • Tothill, R. W., et al. (2008). Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome. Clinical Cancer Research, 14(16), 5198–5208.

    Article  CAS  Google Scholar 

  • Tsujino, T., et al. (2007). Stromal myofibroblasts predict disease recurrence for colorectal cancer. Clinical Cancer Research, 13(7), 2082–2090.

    Article  CAS  Google Scholar 

  • Vanlandewijck, M., et al. (2018). A molecular atlas of cell types and zonation in the brain vasculature. Nature, 554(7693), 475–480.

    Article  CAS  Google Scholar 

  • Viski, C., et al. (2016). Endosialin-expressing pericytes promote metastatic dissemination. Cancer Research, 76(18), 5313–5325.

    Article  CAS  Google Scholar 

  • Xian, X., et al. (2006). Pericytes limit tumor cell metastasis. The Journal of Clinical Investigation, 116(3), 642–651.

    Article  CAS  Google Scholar 

  • Zhuang, L., Lawlor, K. T., Schlueter, H., Pieterse, Z., Yu, Y., & Kaur, P. (2018). Pericytes promote skin regeneration by inducing epidermal cell polarity and planar cell divisions. Life Science Alliance, 1(4), e201700009.

    Article  Google Scholar 

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Authors and Affiliations

  1. Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia

    Zalitha Pieterse & Pritinder Kaur

  2. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

    Devbarna Sinha

Authors
  1. Zalitha Pieterse
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  2. Devbarna Sinha
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  3. Pritinder Kaur
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Correspondence to Pritinder Kaur .

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Editors and Affiliations

  1. Department of Radiology, Columbia University Medical Center, New York, NY, USA

    Alexander Birbrair

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Pieterse, Z., Sinha, D., Kaur, P. (2019). Pericytes in Metastasis. In: Birbrair, A. (eds) Pericyte Biology in Disease. Advances in Experimental Medicine and Biology, vol 1147. Springer, Cham. https://doi.org/10.1007/978-3-030-16908-4_5

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