Acid-mediated tumor invasion as a function of nutrient source location.

Abstract

Cancer cells have an altered metabolism that increases acid production driving to an extracellular pH significantly lower than normal. This leads to normal cell death, and extracellular matrix degradation allowing the formation of an interstitial gap between cancer and healthy cells. In this work, we present a mathematical model to study the interstitial gap formation and evolution considering a tissue with a non-uniform nutrient distribution. Our results indicate that the interstitial gap onsets at the region with highest nutrient consumption. Due to the gap formation, cancer cells near the interface have more nutrient and space availability. This induces cancer cell reproduction and migration toward the nutrient source. Our simulations suggest a strong correlation between gap size and the distance to the nutrient source. Although we do not find a correlation between tumor growth speed and gap size, our results indicate a high risk of metastasis for tumors that develop an interstitial gap, emphasizing the importance of gap detection as a hallmark for cancer invasion.