Why does a tumor start where it does within an organ? Location is traditionally viewed as a random event, yet the statistics tumor locations argue against this. For example, approximately 60% of breast cancer tumors start in the upper outer quadrant of the breast near the armpit, even though it is estimated that only 35% to 40% of the breast tissue is in this quadrant. Similarly, lung cancer occurs ~ 2.5 times more often in the upper than in the lower lobe, even though the upper and lower lobes have roughly the same volume. For colon cancer, almost twice as many tumors originate in the proximal (first half) rather than the distal (second half) colon (excluding the rectum), even though the proximal and distal colons are approximately the same length.
The reasons for these significant location preferences are not understood. This suggests that there is an unknown microenvironmental factor that significantly increases the risk of cancer in a spatial manner and that this is not solely due to genes or toxins.
We hypothesize that tumors are more prone to form at ‘microvascular hot spots’ in healthy tissue
New avenues of research that quantitatively probe the role of physical and spatial properties in tumor formation are necessary to uncover this factor. We believe that the answer lies, in part, in the spatial variations of the vascular network of healthy tissue.
We hypothesize that tumors are more prone to form at ‘microvascular hot spots’ in healthy tissue where there is a higher concentration of blood vessels providing an increased blood flow that ensures an ample supply of oxygen, nutrients, and receptors for growth factors that promote the generation of new blood vessels.
In our paper, published in Cancer Convergence, we focus on breast cancer. To show the plausibility of our hypothesis, we did a simple calculation of the probability that there is at least one hot spot in each region (quadrant) of the breast, assuming a random distribution of microscopic blood vessels. We modulated the microvessel density in various regions of the breast according to the total hemoglobin concentration measured by near infrared diffuse optical spectroscopy in different regions of the breast.
We found good agreement with the observed tumor incidence in different parts of the breast. However, there is no reason to believe that the microvascular distribution is random.
The bottom line is that the spatial location of a tumor is not entirely random, indicating an unknown risk factor. Much work needs to be done to understand why a tumor occurs where it does.
To find out more, read the full paper here.