Pericytes: A Double-Edged Sword in Cancer Therapy

Mao, Meng; Zaorsky, Nicholas G.; Deng, Lei; Wang, Huan Huan; Jiang, Chao; Zhao, Lu; Yuan, Zhi Yong; Wang, Ping

doi:10.2217/fon.14.123

Cited by 65 publications

(58 citation statements)

References 43 publications

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“…The heterogeneity in the endothelial morphology, permeability, and molecular signatures in human and murine mammary tumors (4-6) has highlighted features of tumor angiogenic programs that are under a complex, microenvironment-driven control, in part mediated by pericyte involvement in the tumor vascular bed (7)(8)(9)(10)(11)(12). Defining the regulatory elements that modulate the perivascular-endothelial network to control vessel maturation may offer insights into the clinical response to direct and indirect inhibitors of angiogenesis and unravel antagonistic or synergistic effects of drug combination for the treatment of breast cancer (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

“…Much like cancer cells themselves, the rich microenvironment of breast tumors is highly dynamic and heterogeneous. While pericytes emerge as critical regulators of breast cancer metastasis (3,9,10,16,17), the impact of their heterogeneous composition on breast cancer metastasis and response to chemotherapy is largely unknown. At the core of perivascular-endothelial cell communication, the angiopoietin signaling network, engaging angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) mediated signaling, offers a microenvironmental context-dependent regulation of perivascular recruitment (18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

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Heterogeneous perivascular cell coverage affects breast cancer metastasis and response to chemotherapy

Kim¹,

Sampaio²,

Lundy³

et al. 2016

JCI Insight

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Heterogeneous perivascular cell coverage affects breast cancer metastasis and response to chemotherapy

Kim¹,

Sampaio²,

Lundy³

et al. 2016

JCI Insight

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“…While this indicates that the abrogation of pericytes is a viable therapeutic strategy, the role of pericytes in normalization of the tumor vasculature also must be considered. In the absence of pericytes, vascular permeability and interstitial fluid pressure increases, decreasing tumor perfusion [55]. Consequently, the delivery of drug therapeutics and oxygen is hindered in tumor cells, which promotes cancer cell metastasis [55].…”

Section: Modeling the Complex Tumor Microenvironment In 3dmentioning

confidence: 99%

Heralding a new paradigm in 3D tumor modeling

et al. 2016

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Numerous studies to date have contributed to a paradigm shift in modeling cancer, moving from the traditional two-dimensional culture system to three-dimensional (3D) culture systems for cancer cell culture. This led to the inception of tumor engineering, which has undergone rapid advances over the years. In line with the recognition that tumors are not merely masses of proliferating cancer cells but rather, highly complex tissues consisting of a dynamic extracellular matrix together with stromal, immune and endothelial cells, significant efforts have been made to better recapitulate the tumor microenvironment in 3D. These approaches include the development of engineered matrices and co-cultures to replicate the complexity of tumor-stroma interactions in vitro. However, the tumor engineering and cancer biology fields have traditionally relied heavily on the use of cancer cell lines as a cell source in tumor modeling. While cancer cell lines have contributed to a wealth of knowledge in cancer biology, the use of this cell source is increasingly perceived as a major contributing factor to the dismal failure rate of oncology drugs in drug development. Backing this notion is the increasing evidence that tumors possess intrinsic heterogeneity, which predominantly homogeneous cancer cell lines poorly reflect. Tumor heterogeneity contributes to therapeutic resistance in patients. To overcome this limitation, cancer cell lines are beginning to be replaced by primary tumor cell sources, in the form of patient-derived xenografts and organoids cultures. Moving forward, we propose that further advances in tumor engineering would require that tumor heterogeneity (tumor variants) be taken into consideration together with tumor complexity (tumor-stroma interactions). In this review, we provide a comprehensive overview of what has been achieved in recapitulating tumor complexity, and discuss the importance of incorporating tumor heterogeneity into 3D in vitro tumor models. This work carves out the roadmap for 3D tumor engineering and highlights some of the challenges that need to be addressed as we move forward into the next chapter.

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“…This aberrant pericyte coverage can result in tumor growth and metastasis [88]. Current pericytes-targeted cancer therapies aim to reach a balance between pro-and antiangiogenic factors, encouraging vascular normalization [89].…”

Section: Bmdcsmentioning

confidence: 99%

Anti-VEGF Therapy in Cancer: A Double-Edged Sword

Gardner¹,

Madu²,

Lü³

2017

Physiologic and Pathologic Angiogenesis - Signaling Mechanisms and Targeted Therapy

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Vascular endothelial growth factor (VEGF) is a mitogen that plays a crucial role in angiogenesis and lymphangiogenesis. It is involved in tumor survival through inducing tumor angiogenesis and by increasing chemoresistance through autocrine signaling. Because of its importance in tumor formation and survival, several medications have been developed to inhibit VEGF and reduce blood vessel formation in cancer. Although these medications have proven to be efective for late-stage and metastatic cancers, they have been shown to cause side efects such as hypertension, artery clots, complications in wound healing, and, more rarely, gastrointestinal perforation and istulas. Current research in using anti-VEGF medication as a part of cancer treatments is focusing on elucidating the mechanisms of tumor resistance to VEGF medication, developing predictive biomarkers that assess whether a patient will respond to VEGF therapy and creating novel treatments and techniques that increase the eicacy of antiangiogenic medication. This chapter aims to review the role of VEGF in tumor angiogenesis and metastasis, the structure and function of VEGF and its receptors, and VEGF's role in cancer are discussed. Furthermore, tumor therapies targeting VEGF along with their side efects are presented and, inally, new directions in anti-VEGF therapy are considered along with the challenges.

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Pericytes: A Double-Edged Sword in Cancer Therapy

Cited by 65 publications

References 43 publications

Heterogeneous perivascular cell coverage affects breast cancer metastasis and response to chemotherapy

Heterogeneous perivascular cell coverage affects breast cancer metastasis and response to chemotherapy

Heralding a new paradigm in 3D tumor modeling

Anti-VEGF Therapy in Cancer: A Double-Edged Sword

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