Microcirculation of secondary bone tumors in vivo: The impact of minor surgery at a distal site

Abstract

Microcirculatory properties of tumors play a pivotal role in tumor progression and inefficacy of therapies. It has been hypothesized that surgical interventions result in an accelerated tumor growth by increasing the level of pro-angiogenic cytokines with subsequent amplification of tumor angiogenesis. To characterize the microvascular properties of secondary bone tumors in vivo and determine the impact of minor surgery on the microcirculation, we performed intravital microscopy over 25 days using a xenograft model of breast cancer tumor growth (MCF-7) in bone. After engraftment of tumors the mice were treated with a mastectomy versus no surgery. Tumor growth was accompanied by angiogenic sprouting and decreased vascular diameters while blood flow rate and tumor perfusion remained constant. Mastectomy initially led to a significant reduction of functional vascular density, increased vascular diameter, and decreased blood flow velocities. However, neither tumor growth nor tissue perfusion was different between the groups. The presented study corroborates the assumption that tumor microcirculation in bone exhibits similar time-dependent alterations compared to soft tissue tumors. A minor surgical intervention did not change tumor growth kinetics however microcirculatory properties were altered. Whether major surgery has an impact on tumor growth in bone should be clarified in further studies.

Sunitinib treatment reduces tumor growth and limits changes in microvascular properties after minor surgical intervention in an in vivo model of secondary breast cancer growth in bone

“…Increased engraftment of metastasis [8,16] or accelerated tumor growth has been reported following surgical interventions [17,30]. In our recently published study that was performed under similar conditions to the current study, we reported that minor surgical interventions at a distal site resulted in microvascular alterations and did not change tumor growth kinetics of breast cancer cells in bone [13]. In the aforementioned study, minor surgery resulted in a decrease in the early angiogenic response and microvascular permeability remained constant.…”

“…Increased levels of VEGF result in increased microvascular permeability by loosening intercellular contacts, and decreasing numbers of endothelial cells and increased transcellular openings facilitate the migration of endothelial cells and may lead to pathological extravasation of plasma proteins [31,32]. In the control group, levels of microvascular permeability decreased towards the end of the observation period, corroborating findings from a previous study [13]. The minor surgical intervention did not lead to a significant increase in microvascular permeability; however, in the sunitinib group, a dramatic increase in the level of microvascular permeability was observed on days 8 and 10 following the surgical Fig.…”

“…It has been proposed that these changes influence tumor growth locally and at a distal site through alterations of tumor microcirculation. To what extent increased levels of pro‐angiogenic factors following surgical interventions result in accelerated progression of secondary tumors is controversial . While recent studies show evidence that surgical interventions may induce switching of micrometastases from a dormant state to a rapidly growing tumor , the effect on established metastases has not been thoroughly investigated .…”

“…While recent studies show evidence that surgical interventions may induce switching of micrometastases from a Abbreviations: SCID, severe combined immunodeficient; VD, functional vascular density; D, vascular diameter; SEM, standard error of mean; VEGF, vascular endothelial growth factor; RTK, receptor tyrosine kinases. dormant state to a rapidly growing tumor [14][15][16][17], the effect on established metastases has not been thoroughly investigated [13].…”

3-D Microvessel-Mimicking Ultrasound Phantoms Produced With a Scanning Motion System

“…Indeed, many new imaging techniques are being developed to detect subtle changes in vascularization as a metric for quantifying the effects of administered therapies (Schaefer et al 2010, Pollard and Larson 2010, Hwang et al 2010). Ultrasound is a popular imaging modality for preclinical and clinical disease characterization alike, as it is portable, safe, and relatively inexpensive.…”