Imaging angiogenesis and the microenvironment

Abstract

Intravital microscopy has provided unprecedented insights into tumor pathophysiology, including angiogenesis and the microenvironment. Tumor vasculature shows an abnormal organization, structure, and function. Tumor vessels are leaky, blood flow is heterogeneous and often compromised. Vascular hyperpermeability and the lack of functional lymphatic vessels inside tumors causes elevation of interstitial fluid pressure in solid tumors. These abnormalities form physiological barriers to the delivery of therapeutic agents to tumors and also lead to a hostile microenvironment characterized by hypoxia and acidosis, which hinders the effectiveness of anti-tumor treatments such as radiation therapy and chemotherapy. In addition, host-tumor interactions regulate expression of pro-and antiangiogenic factors, resulting in pathophysiological characteristics of the tumor. On the other hand, in a physiological setting, angiogenic vessels become mature and form long-lasting functional units. Restoring the balance of pro-and anti-angiogenic factors in tumors may ''normalize'' tumor vasculature and thus improve its function. Administration of cytotoxic therapy during the vascular normalization would enhance its efficacy.

Coordinating cell behaviour during blood vessel formation

“…Implantation of specialised imaging 'windows' further allows prolonged analysis of tumour growth and vascularisation without the need for repeated surgery (for reviews, see Fukumura and Jain, 2008;Lohela and Werb, 2010). Advances in microscopy techniques, such as the use of infrared two-photon and second harmonic generation microscopy, allow for deeper tissue imaging and decreased phototoxicity during intravital imaging (Andresen et al, 2009).…”

State-of-the-Art Methods for Evaluation of Angiogenesis and Tissue Vascularization

“…These approaches allow evaluation of structure and intravascular flow velocities, circulating cells, and EC interactions. 204,222 The integration of fluorescence molecular imaging agents with high-resolution in vivo microscopy has facilitated the in vivo serial assessment of angiogenesis and arteriogenesis. 223 Confocal in vivo microscopy can sense events up to 200 μm below the surface.…”

Ricinus communis Agglutinin I Leads to Rapid Down-Regulation of VEGFR-2 and Endothelial Cell Apoptosis in Tumor Blood Vessels

“…[1][2][3] Endothelial cells comprising tumor vessels have abnormalities in gene expression, require growth factors for survival, and have defective barrier function to plasma proteins. 1,3 Molecules that are preferentially expressed on tumor vessels can serve as therapeutic targets. 2 Plant lectins have been used to characterize the surface properties of cells and to isolate membrane proteins of endothelial cells.…”