Population dynamics inside cancer biomass driven by repeated hypoxia-reoxygenation cycles

Chi Zhang, Sha Cao, Ying Xu

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

A computational analysis of genome-scale transcriptomic data collected on ∼1,700 tissue samples of three cancer types: breast carcinoma, colon adenocarcinoma and lung adenocarcinoma, revealed that each tissue consists of (at least) two major subpopulations of cancer cells with different capabilities to handle fluctuating O 2 levels. The two populations have distinct genomic and transcriptomic characteristics, one accelerating its proliferation under hypoxic conditions and the other proliferating faster with higher O 2 levels, referred to as the hypoxia and the reoxygenation subpopulations, respectively. The proportions of the two subpopulations within a cancer tissue change as the average O 2 level changes. They both contribute to cancer development but in a complementary manner. The hypoxia subpopulation tends to have higher proliferation rates than the reoxygenation one as well as higher apoptosis rates; and it is largely responsible for the acidic environment that enables tissue invasion and provides protection against attacks from T-cells. In comparison, the reoxygenation subpopulation generates new extracellular matrices in support of further growth of the tumor and strengthens cell-cell adhesion to provide scaffolds to keep all the cells connected. This subpopulation also serves as the major source of growth factors for tissue growth. These data and observations strongly suggest that these two major subpopulations within each tumor work together in a conjugative relationship to allow the tumor to overcome stresses associated with the constantly changing O 2 level due to repeated growth and angiogenesis. The analysis results not only reveal new insights about the population dynamics within a tumor but also have implications to our understanding of possible causes of different cancer phenotypes such as diffused versus more tightly connected tumor tissues.

Original languageEnglish (US)
Pages (from-to)85-99
Number of pages15
JournalQuantitative Biology
Volume2
Issue number3
DOIs
StatePublished - Sep 1 2014
Externally publishedYes

Fingerprint

Hypoxia
Population dynamics
Population Dynamics
Biomass
Tumor
Cancer
Tumors
Tissue
Cycle
Neoplasms
Proliferation
Cell
Cell Adhesion
Angiogenesis
Apoptosis
Scaffold
Computational Analysis
Growth Factors
Invasion
T-cells

Keywords

  • cancer cell subpopulations
  • cancer evolution
  • cancer population dynamics
  • hypoxia
  • intratumor heterogeneity
  • reoxygenation

ASJC Scopus subject areas

  • Modeling and Simulation
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Computer Science Applications
  • Applied Mathematics

Cite this

Population dynamics inside cancer biomass driven by repeated hypoxia-reoxygenation cycles. / Zhang, Chi; Cao, Sha; Xu, Ying.

In: Quantitative Biology, Vol. 2, No. 3, 01.09.2014, p. 85-99.

Research output: Contribution to journalArticle

@article{05db404a7ea24709bf5c67b49ef51b08,
title = "Population dynamics inside cancer biomass driven by repeated hypoxia-reoxygenation cycles",
abstract = "A computational analysis of genome-scale transcriptomic data collected on ∼1,700 tissue samples of three cancer types: breast carcinoma, colon adenocarcinoma and lung adenocarcinoma, revealed that each tissue consists of (at least) two major subpopulations of cancer cells with different capabilities to handle fluctuating O 2 levels. The two populations have distinct genomic and transcriptomic characteristics, one accelerating its proliferation under hypoxic conditions and the other proliferating faster with higher O 2 levels, referred to as the hypoxia and the reoxygenation subpopulations, respectively. The proportions of the two subpopulations within a cancer tissue change as the average O 2 level changes. They both contribute to cancer development but in a complementary manner. The hypoxia subpopulation tends to have higher proliferation rates than the reoxygenation one as well as higher apoptosis rates; and it is largely responsible for the acidic environment that enables tissue invasion and provides protection against attacks from T-cells. In comparison, the reoxygenation subpopulation generates new extracellular matrices in support of further growth of the tumor and strengthens cell-cell adhesion to provide scaffolds to keep all the cells connected. This subpopulation also serves as the major source of growth factors for tissue growth. These data and observations strongly suggest that these two major subpopulations within each tumor work together in a conjugative relationship to allow the tumor to overcome stresses associated with the constantly changing O 2 level due to repeated growth and angiogenesis. The analysis results not only reveal new insights about the population dynamics within a tumor but also have implications to our understanding of possible causes of different cancer phenotypes such as diffused versus more tightly connected tumor tissues.",
keywords = "cancer cell subpopulations, cancer evolution, cancer population dynamics, hypoxia, intratumor heterogeneity, reoxygenation",
author = "Chi Zhang and Sha Cao and Ying Xu",
year = "2014",
month = "9",
day = "1",
doi = "10.1007/s40484-014-0032-8",
language = "English (US)",
volume = "2",
pages = "85--99",
journal = "Quantitative Biology",
issn = "2095-4689",
publisher = "Higher Education Press",
number = "3",

}

TY - JOUR

T1 - Population dynamics inside cancer biomass driven by repeated hypoxia-reoxygenation cycles

AU - Zhang, Chi

AU - Cao, Sha

AU - Xu, Ying

PY - 2014/9/1

Y1 - 2014/9/1

N2 - A computational analysis of genome-scale transcriptomic data collected on ∼1,700 tissue samples of three cancer types: breast carcinoma, colon adenocarcinoma and lung adenocarcinoma, revealed that each tissue consists of (at least) two major subpopulations of cancer cells with different capabilities to handle fluctuating O 2 levels. The two populations have distinct genomic and transcriptomic characteristics, one accelerating its proliferation under hypoxic conditions and the other proliferating faster with higher O 2 levels, referred to as the hypoxia and the reoxygenation subpopulations, respectively. The proportions of the two subpopulations within a cancer tissue change as the average O 2 level changes. They both contribute to cancer development but in a complementary manner. The hypoxia subpopulation tends to have higher proliferation rates than the reoxygenation one as well as higher apoptosis rates; and it is largely responsible for the acidic environment that enables tissue invasion and provides protection against attacks from T-cells. In comparison, the reoxygenation subpopulation generates new extracellular matrices in support of further growth of the tumor and strengthens cell-cell adhesion to provide scaffolds to keep all the cells connected. This subpopulation also serves as the major source of growth factors for tissue growth. These data and observations strongly suggest that these two major subpopulations within each tumor work together in a conjugative relationship to allow the tumor to overcome stresses associated with the constantly changing O 2 level due to repeated growth and angiogenesis. The analysis results not only reveal new insights about the population dynamics within a tumor but also have implications to our understanding of possible causes of different cancer phenotypes such as diffused versus more tightly connected tumor tissues.

AB - A computational analysis of genome-scale transcriptomic data collected on ∼1,700 tissue samples of three cancer types: breast carcinoma, colon adenocarcinoma and lung adenocarcinoma, revealed that each tissue consists of (at least) two major subpopulations of cancer cells with different capabilities to handle fluctuating O 2 levels. The two populations have distinct genomic and transcriptomic characteristics, one accelerating its proliferation under hypoxic conditions and the other proliferating faster with higher O 2 levels, referred to as the hypoxia and the reoxygenation subpopulations, respectively. The proportions of the two subpopulations within a cancer tissue change as the average O 2 level changes. They both contribute to cancer development but in a complementary manner. The hypoxia subpopulation tends to have higher proliferation rates than the reoxygenation one as well as higher apoptosis rates; and it is largely responsible for the acidic environment that enables tissue invasion and provides protection against attacks from T-cells. In comparison, the reoxygenation subpopulation generates new extracellular matrices in support of further growth of the tumor and strengthens cell-cell adhesion to provide scaffolds to keep all the cells connected. This subpopulation also serves as the major source of growth factors for tissue growth. These data and observations strongly suggest that these two major subpopulations within each tumor work together in a conjugative relationship to allow the tumor to overcome stresses associated with the constantly changing O 2 level due to repeated growth and angiogenesis. The analysis results not only reveal new insights about the population dynamics within a tumor but also have implications to our understanding of possible causes of different cancer phenotypes such as diffused versus more tightly connected tumor tissues.

KW - cancer cell subpopulations

KW - cancer evolution

KW - cancer population dynamics

KW - hypoxia

KW - intratumor heterogeneity

KW - reoxygenation

UR - http://www.scopus.com/inward/record.url?scp=84945583025&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84945583025&partnerID=8YFLogxK

U2 - 10.1007/s40484-014-0032-8

DO - 10.1007/s40484-014-0032-8

M3 - Article

AN - SCOPUS:84945583025

VL - 2

SP - 85

EP - 99

JO - Quantitative Biology

JF - Quantitative Biology

SN - 2095-4689

IS - 3

ER -