A combined microfluidic-transcriptomic approach to characterize the extravasation potential of cancer cells

Simone Bersini, Agnes Miermont, Andrea Pavesi, Roger Dale Kamm, Jean Paul Thiery, Matteo Moretti, Giulia Adriani

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The reciprocal interaction between circulating tumor cells (CTCs) and tissue-specific cells is influential for the progression of metastases. In particular, the process of extravasation relies on the complex cross-talk between cancer cells and other cellular players such as the endothelium and the secondary tissue. However, most in vitro studies only focus on one heterotypic cell-cell interaction and often lack of physiological relevance. In this project, we investigated both CTC-endothelium and CTC-secondary site interactions during cancer cell extravasation. We first used a microarray analysis of extravasated MDA-MB-231 breast cancer cells to identify key markers involved in extravasation. Then, we developed a tri-culture microfluidic platform combining cancer cells, endothelium and a bone-mimicking (BMi) microenvironment to assess how organ tropism influences the extravasation potential of cancer cells from different tissues. Through the microarray analyses of extravasated cancer cells we found that extravasation is associated with upregulation of late-metastatic markers along with specific proteases, such as matrix metalloprotease (MMP), a-disintegrin and metalloprotease (ADAM) and a-disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family members, which are all involved in endothelium glycocalyx shedding. Through the microfluidic extravasation assay, we found that the bone-like microenvironment increased invasion and motility of breast, bladder and ovarian cancer cell (MDA-MB-231, T24 and OVCAR-3). Among the three cell types, ovarian cancer cells presented the lowest migration rate and bladder cancer cells the highest, hence recapitulating their different level of bone tropism observed in vivo. Taken together, our results shed light on the importance of intercellular communication between CTCs and other non-tumor cells essential for promoting cancer cell extravasation.

Original languageEnglish
Pages (from-to)36110-36125
Number of pages16
JournalOncotarget
Volume9
Issue number90
Publication statusPublished - Nov 1 2018

Fingerprint

Microfluidics
Neoplasms
Circulating Neoplastic Cells
Endothelium
Metalloproteases
Disintegrins
Tropism
Microarray Analysis
Urinary Bladder Neoplasms
Bone and Bones
Ovarian Neoplasms
Breast Neoplasms
Thrombospondins
Glycocalyx
Cell Communication

Keywords

  • Cancer cell extravasation
  • Microarrays
  • Microfluidics
  • Organ-specific metastasis
  • Tumor microenvironment

ASJC Scopus subject areas

  • Oncology

Cite this

Bersini, S., Miermont, A., Pavesi, A., Kamm, R. D., Thiery, J. P., Moretti, M., & Adriani, G. (2018). A combined microfluidic-transcriptomic approach to characterize the extravasation potential of cancer cells. Oncotarget, 9(90), 36110-36125.

A combined microfluidic-transcriptomic approach to characterize the extravasation potential of cancer cells. / Bersini, Simone; Miermont, Agnes; Pavesi, Andrea; Kamm, Roger Dale; Thiery, Jean Paul; Moretti, Matteo; Adriani, Giulia.

In: Oncotarget, Vol. 9, No. 90, 01.11.2018, p. 36110-36125.

Research output: Contribution to journalArticle

Bersini, S, Miermont, A, Pavesi, A, Kamm, RD, Thiery, JP, Moretti, M & Adriani, G 2018, 'A combined microfluidic-transcriptomic approach to characterize the extravasation potential of cancer cells', Oncotarget, vol. 9, no. 90, pp. 36110-36125.
Bersini S, Miermont A, Pavesi A, Kamm RD, Thiery JP, Moretti M et al. A combined microfluidic-transcriptomic approach to characterize the extravasation potential of cancer cells. Oncotarget. 2018 Nov 1;9(90):36110-36125.
Bersini, Simone ; Miermont, Agnes ; Pavesi, Andrea ; Kamm, Roger Dale ; Thiery, Jean Paul ; Moretti, Matteo ; Adriani, Giulia. / A combined microfluidic-transcriptomic approach to characterize the extravasation potential of cancer cells. In: Oncotarget. 2018 ; Vol. 9, No. 90. pp. 36110-36125.
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