Angiogenesis in Cancer

Cancer cells’ survival critically depends on vasculature and blood supply which provide essential nutrients and oxygen to support the typically accelerated tumor growth. Additionally, vascular structures (e.g., new vessels, pre-existing vessels and vessel-like structures) allow cancer cells to travel to distant tissues and organs supporting cancer spread. Formation of new vasculature, or angiogenesis, is therefore a process that contributes to tumor growth and metastasis and is particularly critical for solid tumors.

“Angiogenic switch” refers to the activation of molecular pathways that direct the formation of new vessels within a tumor. Specific genetic changes in tumor cells underscore the activation of angiogenic programs by tilting the balance between the activity of angiogenic activators and inhibitors.

Angiogenic switch, inhibitors and activators

Angiogenic switch
A shift in the balance between the activities of angiogenesis inhibitors and activators underscores the angiogenic switch which allows solid tumors to sustain their growth beyond 2-3 mm diameter.

Within the angiogenesis cascade, different molecular factors play key roles in the establishment of new vessels. For example, VEGF is a critical angiogenic growth factor which stimulates the proliferation and survival of endothelial cells. In the tumor microenvironment, VEGF expression may be stimulated by hypoxia via the stabilization and activity of HIF transcription factors. Release of VEGF stimulates the concomitant secretion of proteases (e.g., Metalloproteinases- MMP-9) by endothelial cells of mature vessels which degrade the extracellular basement membrane and facilitate the movement and proliferation of endothelial cells. Under the influence of VEGF and other growth factors as well as adhesion molecules (e.g., Integrins) endothelial cells proliferate and migrate to give rise to new vessels.

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Angiopoietin-1 expression in human prostate cancer, IHC VEGF expression in human breast cancer, IHC

VEGF was detected in immersion fixed paraffin-embedded sections of human breast cancer tissue using Human VEGF 165 Polyclonal Antibody (Catalog # AB-293-NA) at 15 µg/mL overnight at 4 °C. Tissue was stained using the Anti-Goat HRP-DAB Cell & Tissue Staining Kit (brown; Catalog # CTS008) and counterstained with hematoxylin (blue). Lower panel shows a lack of labeling if primary antibodies are omitted and tissue is stained only with secondary antibody followed by incubation with detection reagents.

Angiopoietin-1 was detected in immersion fixed paraffin-embedded sections of human prostate cancer tissue using 15 µg/mL Goat Anti-Human/Mouse Angiopoietin-1 Antigen Affinity-purified Polyclonal Antibody (Catalog # AF923) overnight at 4 °C. Tissue was stained with the Anti-Goat HRP-DAB Cell & Tissue Staining Kit (brown; Catalog # CTS008) and counterstained with hematoxylin (blue).

Endogenous Modulators of Angiogenesis

Angiogenic Modulators




Myc, Ras, Her2

Growth factors

VEGF-A, FGF, PDGF, EGF, Angiopoietin-1


IL-1 alpha,  IL-1 beta, TNF-alpha, IL-8

IL-4, IL-10, IL-12IFN-alpha

Microenvironmental factors


Transcription factors

HIF-1 alpha, HIF-2 alpha

Other modulators

Thrombospondin-1, Chitinase-3-like 1, sFRP-4, Angiopoietin-2, TIMP

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Select References

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Ksenya, S., & Gerard, Evan. (2007). Tumor Angiogenesis: Cause or Consequence of Cancer? Cancer Res.

Muley, A., Majumder, S., Kolluru, G. K., Parkinson, S., Viola, H., Hool, L., … Chatterjee, S. (2010). Secreted frizzled-related protein 4: An angiogenesis inhibitor. American Journal of Pathology.

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Pezzella, F., Gatter, K., & Qian, C. N. (2016). Twenty years after: The beautiful hypothesis and the ugly facts. Chinese Journal of Cancer.

Qian, C. N., Tan, M. H., Yang, J. P., & Cao, Y. (2016). Revisiting tumor angiogenesis: Vessel co-option, vessel remodeling, and cancer cell-derived vasculature formation. Chinese Journal of Cancer.

 Rak, J., Yu, J. L., Klement, G., & Kerbel, R. S. (2000). Oncogenes and angiogenesis: Signaling three-dimensional tumor growth. Journal of Investigative Dermatology Symposium Proceedings.

Yadav, L., Puri, N., Rastogi, V., Satpute, P., & Sharma, V. (2015). Tumour angiogenesis and angiogenic inhibitors: A review. Journal of Clinical and Diagnostic Research.