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The Tumor Microenvironment

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...

The Tumor Microenvironment

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...

Regulation of Angiogenesis and Blood Supply

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...

Mechanism of Angiogenesis

Mechanism of Angiogenesis

Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...

Adaptive Mechanisms in Cancer Cells

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...

Adaptive Mechanisms in Cancer Cells

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...

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Related Experiment Video

Updated: Jul 6, 2026

Establishing a Physiologic Human Vascularized Micro-Tumor Model for Cancer Research

Establishing a Physiologic Human Vascularized Micro-Tumor Model for Cancer Research

Published on: September 15, 2023

Vascular reprogramming in cancer: engineering the tumor microenvironment.

Yusuke Nishimura¹

¹Department of Medical Technology and Clinical Engineering, Faculty of Medical Technology and Clinical Engineering, Gunma University of Health and Welfare, 191-1 Kawamagari-Cho, Maebashi City, Gunma, 371-0823, Japan. y-nishi@kitasato-u.ac.jp.

|July 5, 2026

Summary

Tumor vasculature actively shapes the tumor microenvironment. Vascular reprogramming offers a new therapeutic strategy to engineer blood vessels for better cancer control and treatment, moving beyond traditional inhibition methods.

Keywords:

Organoid-on-a-chip Tumor microenvironment Tumor vasculature Vascular niche Vascular reprogramming

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Isolation and Culture Expansion of Tumor-specific Endothelial Cells

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Last Updated: Jul 6, 2026

Establishing a Physiologic Human Vascularized Micro-Tumor Model for Cancer Research

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Published on: September 15, 2023

Assessing Tumor Microenvironment of Metastasis Doorway-Mediated Vascular Permeability Associated with Cancer Cell Dissemination using Intravital Imaging and Fixed Tissue Analysis

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Isolation and Culture Expansion of Tumor-specific Endothelial Cells

Isolation and Culture Expansion of Tumor-specific Endothelial Cells

Published on: October 14, 2015

Area of Science:

Vascular biology
Regenerative medicine
Bioengineering
Cancer therapy

Background:

Traditionally, tumor vasculature was targeted for inhibition due to its abnormal structure and function.
Emerging evidence suggests blood vessels actively instruct and shape the tumor microenvironment, challenging this paradigm.

Purpose of the Study:

Propose tumor vasculature as a dynamic, programmable interface regulating cancer progression.
Define vascular reprogramming as a therapeutic strategy to redesign vascular structure, function, and signaling.
Position the vasculature as a central regulatory hub in the tumor ecosystem.

Main Methods:

Integrating advances in endothelial cell heterogeneity, vascular niche biology, and multiscale modeling.
Utilizing enabling technologies like vascularized organoids, organ-on-a-chip systems, and iPSC-derived vasculature.
Distinguishing vascular reprogramming from conventional anti-angiogenic and normalization strategies.

Main Results:

Tumor vessels govern cancer stemness, immune-cell trafficking, and metabolic adaptation.
Vascular reprogramming enhances drug delivery, improves immune infiltration, and increases therapeutic sensitivity.
This approach offers sustained and integrative control of the tumor microenvironment.

Conclusions:

Tumor vasculature is a designable therapeutic interface.
Vascular reprogramming represents a new paradigm in cancer therapy: engineering the tumor microenvironment through vascular control.
Future directions include addressing clinical translation challenges and leveraging spatial omics and AI.