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Autocrine signaling can explain the emergence of Allee effects in cancer cell populations.

ABSTRACT: In many human cancers, the rate of cell growth depends crucially on the size of the tumor cell population. Low, zero, or negative growth at low population densities is known as the Allee effect; this effect has been studied extensively in ecology, but so far lacks a good explanation in the cancer setting. Here, we formulate and analyze an individual-based model of cancer, in which cell division rates are increased by the local concentration of an autocrine growth factor produced by the cancer cells themselves. We show, analytically and by simulation, that autocrine signaling suffices to cause both strong and weak Allee effects. Whether low cell densities lead to negative (strong effect) or reduced (weak effect) growth rate depends directly on the ratio of cell death to proliferation, and indirectly on cellular dispersal. Our model is consistent with experimental observations from three patient-derived brain tumor cell lines grown at different densities. We propose that further studying and quantifying population-wide feedback, impacting cell growth, will be central for advancing our understanding of cancer dynamics and treatment, potentially exploiting Allee effects for therapy.

SUBMITTER: Gerlee P

PROVIDER: S-EPMC8923455 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Autocrine signaling can explain the emergence of Allee effects in cancer cell populations.

Gerlee Philip P Altrock Philipp M PM Malik Adam A Krona Cecilia C Nelander Sven S

PLoS computational biology 20220303 3

In many human cancers, the rate of cell growth depends crucially on the size of the tumor cell population. Low, zero, or negative growth at low population densities is known as the Allee effect; this effect has been studied extensively in ecology, but so far lacks a good explanation in the cancer setting. Here, we formulate and analyze an individual-based model of cancer, in which cell division rates are increased by the local concentration of an autocrine growth factor produced by the cancer ce ...[more]

PMID: 35239640

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Project description:We consider the spatial propagation and genetic evolution of model populations comprising multiple subpopulations, each distinguished by its own characteristic dispersal rate. Mate finding is modeled in accord with the assumption that reproduction is based on random encounters between pairs of individuals, so that the frequency of interbreeding between two subpopulations is proportional to the product of local population densities of each. The resulting nonlinear growth term produces an Allee effect, whereby reproduction rates are lower in sparsely populated areas; the distribution of dispersal rates that evolves is then highly dependent upon the population's initial spatial distribution. In a series of numerical test cases, we consider how these dynamics affect lattice-like arrangements of population fragments, and investigate how a population's initial fragmentation determines the dispersal rates that evolve as a habitat is colonized. First, we consider a case where initial population fragments coincide with habitat islands, within which death rates differ from those that apply outside; the presence of inhospitable exterior regions exaggerates Allee effect-driven reductions in dispersal ability. We then examine how greater distances separating adjacent population fragments lead to more severe reductions in dispersal ability. For populations of a fixed initial magnitude, fragmentation into smaller, denser patches leads not only to greater losses of dispersal ability, but also helps ensure the population's long-term persistence, emphasizing the trade-offs between the benefits and risks of rapid dispersal under Allee effects. Next, simulations of well-established populations disrupted by localized depopulation events illustrate how mate-finding Allee effects and spatial heterogeneity can drive a population's dispersal ability to evolve either downward or upward depending on conditions, highlighting a qualitative distinction between population fragmentation and habitat heterogeneity. A final test case compares populations that are fragmented across multiple scales, demonstrating how differences in the relative scales of micro- and macro-level fragmentation can lead to qualitatively different evolutionary outcomes.

Dataset Information

Autocrine signaling can explain the emergence of Allee effects in cancer cell populations.

Publications

Autocrine signaling can explain the emergence of Allee effects in cancer cell populations.

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