Accessory Cells in Tumor Angiogenesis — Tumor-Associated Pericytes

Minami, Yoshinori; Sasaki, Tatsuya; Kawabe, Jun‐ichi; Ohsaki, Yoshinobu

doi:10.5772/54523

Cited by 4 publications

(3 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been documented that the endothelial cells on the tip of newly sprouted vascular channel recruit pericytes via secretion of PDGF-BB. This factor activates the pericytes by binding with PDGFR-β receptors expressed on the pericyte surface and induce its migration across the sprouted vascular channel, thereby modulating the pericyte coverage on tumor vessels (Armulik et al, 2011 ; Minami et al, 2013 ).…”

Section: Understanding the Challenges And Opportunities Presented By mentioning

confidence: 99%

Tumor Microenvironment Targeted Nanotherapy

2018

View full text Add to dashboard Cite

Recent developments in nanotechnology have brought new approaches to cancer diagnosis and therapy. While enhanced permeability and retention effect promotes nano-chemotherapeutics extravasation, the abnormal tumor vasculature, high interstitial pressure and dense stroma structure limit homogeneous intratumoral distribution of nano-chemotherapeutics and compromise their imaging and therapeutic effect. Moreover, heterogeneous distribution of nano-chemotherapeutics in non-tumor-stroma cells damages the non-tumor cells, and interferes with tumor-stroma crosstalk. This can lead not only to inhibition of tumor progression, but can also paradoxically induce acquired resistance and facilitate tumor cell proliferation and metastasis. Overall, the tumor microenvironment plays a vital role in regulating nano-chemotherapeutics distribution and their biological effects. In this review, the barriers in tumor microenvironment, its consequential effects on nano-chemotherapeutics, considerations to improve nano-chemotherapeutics delivery and combinatory strategies to overcome acquired resistance induced by tumor microenvironment have been summarized. The various strategies viz., nanotechnology based approach as well as ligand-mediated, redox-responsive, and enzyme-mediated based combinatorial nanoapproaches have been discussed in this review.

show abstract

Section: Understanding the Challenges And Opportunities Presented By mentioning

confidence: 99%

Tumor Microenvironment Targeted Nanotherapy

2018

View full text Add to dashboard Cite

show abstract

“…Metastatic disease remains the leading cause of ccRCC-related deaths with the most common sites being the lungs, bones, and lymph nodes (2,13). Vascular stabilization and enhanced pericyte recruitment, while often reported to enhance tumor growth, have been recently linked to inhibition of tumor metastases, suggesting a dual potential role for the inhibition and stabilization of vasculature by pericytes (8,(14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

Dual Inhibition of Angiopoietin-TIE2 and MET Alters the Tumor Microenvironment and Prolongs Survival in a Metastatic Model of Renal Cell Carcinoma

Elbanna

Orillion

Damayanti

et al. 2020

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Receptor tyrosine kinase inhibitors have shown clinical benefit in clear cell renal cell carcinoma (ccRCC), but novel therapeutic strategies are needed. The angiopoietin/Tie2 and MET pathways have been implicated in tumor angiogenesis, metastases, and macrophage infiltration. In our study, we used trebananib, an angiopoietin 1/2 inhibitor, and a novel small-molecule MET kinase inhibitor in patient-derived xenograft (PDX) models of ccRCC. Our goal was to assess the ability of these compounds to alter the status of tumor-infiltrating macrophages, inhibit tumor growth and metastases, and prolong survival. Seven-week-old SCID mice were implanted subcutaneously or orthotopically with human ccRCC models. One month postimplantation, mice were treated with angiopoietin 1/2 inhibitor trebananib (AMG 386), MET kinase inhibitor, or combination. In our metastatic ccRCC PDX model, RP-R-02LM, trebananib alone, and in combination with a MET kinase inhibitor, significantly reduced lung metastases and M2 macrophage infiltration (P ¼ 0.0075 and P ¼ 0.0205, respectively). Survival studies revealed that treatment of the orthotopically implanted RP-R-02LM tumors yielded a significant increase in survival in both trebananib and combination groups. In addition, resection of the subcutaneously implanted primary tumor allowed for a significant survival advantage to the combination group compared with vehicle and both single-agent groups. Our results show that the combination of trebananib with a MET kinase inhibitor significantly inhibits the spread of metastases, reduces infiltrating M2-type macrophages, and prolongs survival in our highly metastatic ccRCC PDX model, suggesting a potential use for this combination therapy in treating patients with ccRCC.

show abstract

“…In cancer, the tumor vascular structure does not achieve proper maturation and, as a consequence, has several abnormalities including irregular pericyte coverage [ 14 ]. Furthermore, tumor pericytes are loosely attached to the endothelium and present aberrant cytoplasmic projections invading the tumor parenchyma [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Lysyl Oxidases Impairs Migration and Angiogenic Properties of Tumor-Associated Pericytes

Ribeiro

Kaid

Silva

et al. 2017

Stem Cells International

View full text Add to dashboard Cite

Pericytes are important cellular components of the tumor microenviroment with established roles in angiogenesis and metastasis. These two cancer hallmarks are modulated by enzymes of the LOX family, but thus far, information about LOX relevance in tumor-associated pericytes is lacking. Here, we performed a comparative characterization of normal and tumoral pericytes and report for the first time the modulatory effects of LOX enzymes on activated pericyte properties. Tumoral pericytes isolated from childhood ependymoma and neuroblastoma specimens displayed angiogenic properties in vitro and expressed typical markers, including CD146, NG2, and PDGFRβ. Expression of all LOX family members could be detected in both normal and tumor-associated pericytes. In most pericyte samples, LOXL3 was the family member displaying the highest transcript levels. Inhibition of LOX/LOXL activity with the inhibitor β-aminopropionitrile (βAPN) significantly reduced migration of pericytes, while proliferation rates were kept unaltered. Formation of tube-like structures in vitro by pericytes was also significantly impaired upon inhibition of LOX/LOXL activity with βAPN, which induced more prominent effects in tumor-associated pericytes. These findings reveal a novel involvement of the LOX family of enzymes in migration and angiogenic properties of pericytes, with implications in tumor development and in therapeutic targeting tumor microenvironment constituents.

show abstract

Accessory Cells in Tumor Angiogenesis — Tumor-Associated Pericytes

Cited by 4 publications

References 85 publications

Tumor Microenvironment Targeted Nanotherapy

Tumor Microenvironment Targeted Nanotherapy

Dual Inhibition of Angiopoietin-TIE2 and MET Alters the Tumor Microenvironment and Prolongs Survival in a Metastatic Model of Renal Cell Carcinoma

Inhibition of Lysyl Oxidases Impairs Migration and Angiogenic Properties of Tumor-Associated Pericytes

Contact Info

Product

Resources

About