Figure 1

(a) Representative image from intravital multiphoton microscopy of perfused tumour vessels (green) and collagen (blue), showing that high collagen levels colocalize with low perfusion in an E0771 breast tumour. Scale bar, 200 μm. (b) Histology images of vascular perfusion in orthotopic AK4.4 pancreatic tumours with high versus low collagen levels. High local collagen I levels (blue) appear to colocalize with collapsed vessels (red, collapsed; green/yellow, perfused) in vivo. Scale bar, 100 μm. (c) Correlation of perfused vessel fraction versus tumour matrix area fractions in multiple orthotopic pancreatic tumour models (AK4.4 and L3.6pl) in mice. Following lectin injection and animal killing, perfusion was quantified as the fraction of vessels that are both lectin- and CD31-positive out of all CD31-positive vessels. Perfusion inversely correlates with both hyaluronan (R=−0.79, P<0.001, Pearson’s correlation) and collagen I (R=−0.78, P<0.001, Pearson’s correlation), but has a stronger inverse correlation (R=−0.86, P<0.001, Pearson’s correlation) with the average matrix area fraction. (d) Grouping these tumours into those with either low (<17%) or high (≥17%) collagen reveals that perfusion does not correlate (R=−0.33, Pearson’s correlation) with hyaluronan in collagen-poor tumours but does inversely correlate (R=−0.71, P=0.004, Pearson’s correlation) in collagen-rich tumours. (e) In contrast, grouping the tumours into those with either low (<33%) or high (≥33%) hyaluronan shows that perfusion inversely correlates with collagen I in both hyaluronan-poor (R=−0.73, P=0.003, Pearson’s correlation) and hyaluronan-rich (R=−0.57, P=0.040, Pearson’s correlation) tumours.