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Bulletin of Mathematical Biology

, Volume 80, Issue 5, pp 1046–1058 | Cite as

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

  • Arturo AraujoEmail author
  • Leah M. Cook
  • Conor C. Lynch
  • David BasantaEmail author
Special Issue : Mathematical Oncology

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.

Keywords

Bone Metastases Cancer Agent-based Prostate cancer 

Notes

Acknowledgements

We would like to acknowledge Dr. Anderson from Moffitt’s Integrated Mathematical Oncology Department for helpful discussions. AA, LC, CCL and DB were partly funded by an NCI U01 (NCI) U01CA202958-01 and a Moffitt Team Science Award. AA was partly funded by a Department of Defense Prostate Cancer Research Program (W81XWH-15-1-0184) fellowship. LC was partly funded by a postdoctoral fellowship (PF-13-175-01-CSM) from the American Cancer Society.

Compliance with Ethical Standards

Conflict of interest

None.

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Copyright information

© Society for Mathematical Biology 2018

Authors and Affiliations

  1. 1.Integrated Mathematical OncologyH. Lee Moffitt Cancer Center and Research InstituteTampaUSA
  2. 2.Tumor Biology DepartmentH. Lee Moffitt Cancer Center and Research InstituteTampaUSA

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