Size Matters: Metastatic Cluster Size and Stromal Recruitment in the Establishment of Successful Prostate Cancer to Bone Metastases

Arturo Araujo, Leah M. Cook, Conor C. Lynch, David Basanta

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Prostate cancer (PCa) impacts over 180,000 men every year in the USA alone, with 26,000 patients expected to succumb to the disease (cancer.gov). The primary cause of death is metastasis, with secondary lesions most commonly occurring in the skeleton. Prostate cancer to bone metastasis is an important, yet poorly understood, process that is difficult to explore with experimental techniques alone. To this end we have utilized a hybrid (discrete–continuum) cellular automaton model of normal bone matrix homeostasis that allowed us to investigate how metastatic PCa can disrupt the bone microenvironment. Our previously published results showed that PCa cells can recruit mesenchymal stem cells (MSCs) that give rise to bone-building osteoblasts. MSCs are also thought to be complicit in the establishment of successful bone metastases (Lu, in Mol Cancer Res 4(4):221–233, 2006). Here we have explored the aspects of early metastatic colonization and shown that the size of PCa clusters needs to be within a specific range to become successfully established: sufficiently large to maximize success, but not too large to risk failure through competition among cancer and stromal cells for scarce resources. Furthermore, we show that MSC recruitment can promote the establishment of a metastasis and compensate for relatively low numbers of PCa cells seeding the bone microenvironment. Combined, our results highlight the utility of biologically driven computational models that capture the complex and dynamic dialogue between cells during the initiation of active metastases.

Original languageEnglish (US)
Pages (from-to)1046-1058
Number of pages13
JournalBulletin of Mathematical Biology
Volume80
Issue number5
DOIs
StatePublished - May 1 2018

Fingerprint

Bone Neoplasms
Prostate Cancer
Metastasis
prostatic neoplasms
Bone
metastasis
bone
cancer
Prostatic Neoplasms
bones
Neoplasm Metastasis
Stem Cells
Stem cells
Mesenchymal Stromal Cells
stem cells
Bone and Bones
Cancer
Cell
stem
Hybrid Automata

Keywords

  • Agent-based
  • Bone
  • Cancer
  • Metastases
  • Prostate cancer

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Mathematics(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Environmental Science(all)
  • Pharmacology
  • Agricultural and Biological Sciences(all)
  • Computational Theory and Mathematics

Cite this

Size Matters : Metastatic Cluster Size and Stromal Recruitment in the Establishment of Successful Prostate Cancer to Bone Metastases. / Araujo, Arturo; Cook, Leah M.; Lynch, Conor C.; Basanta, David.

In: Bulletin of Mathematical Biology, Vol. 80, No. 5, 01.05.2018, p. 1046-1058.

Research output: Contribution to journalArticle

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