Increased cell size, structural complexity and migration of cancer cells acquiring fibroblast organelles by cell-projection pumping


Autoři: Hans Zoellner aff001;  Belal Chami aff001;  Elizabeth Kelly aff001;  Malcolm A. S. Moore aff002
Působiště autorů: The Cellular and Molecular Pathology Research Unit, Oral Pathology and Oral Medicine, School of Dentistry, Faculty of Medicine and Health, The University of Sydney, Westmead Hospital, Westmead, NSW, Australia aff001;  Cell Biology, The Memorial Sloan Kettering Cancer Center, New York, NY, United States of America aff002
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224800

Souhrn

We recently described a hydrodynamic mechanism for cytoplasmic transfer between cells, termed cell-projection pumping (CPP). Earlier image analysis related altered SAOS-2 osteosarcoma cell morphology, to what we now recognize as CPP uptake of fibroblast cytoplasm. We here examine SAOS-2 phenotype following co-culture with human dermal fibroblasts (HDF) in which organelles were pre-labelled with a fluorescent lipophilic marker. Fluorescence activated cell sorting (FACS) analysis was performed of HDF and SAOS-2, cultured either alone or together. FACS forward scatter is proportionate to cell size, and increased for SAOS-2 with high levels of HDF fluorescence uptake (p < 0.004). FACS side scatter is proportionate to internal cell complexity, and increased in SAOS-2 with increasing uptake of HDF fluorescence (p < 0.004), consistent with uptake of HDF organelles. Scratch migration assays revealed that HDF migrated more quickly than SAOS-2 in both isolated cell culture, and following co-culture (p < 0.004). Notably, SAOS-2 with high levels of HDF labelling migrated faster compared with SAOS-2 with low HDF labelling (p < 0.008). A slight and unconvincing reduction in SAOS-2 proliferation was seen (p < 0.02). Similar results were obtained in single additional experiments with A673 and H312 cancer cells. Forward and side scatter results suggest organellar transfer by CPP increases cancer cell morphological diversity. This may contribute to histological pleomorphism relevant to cancer diagnosis and prognosis. Also, increased migration of sub-populations of cancer cells with high CPP organellar uptake, may contribute to invasion and metastasis in-vivo. We thus suggest relevance of CPP to cancer diagnosis and progression.

Klíčová slova:

Cancer cell migration – Cellular structures and organelles – Cytoplasm – Exosomes – Fibroblasts – Fluorescence microscopy – Membrane proteins – Fluorescence-activated cell sorting


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2019 Číslo 11