2012 ADIA Research Grant - Australian Dental Research Foundation
The Australian Dental Industry Association (ADIA) is pleased to announce that Associate Professor Hans Zoellner from the University of Sydney is the recipient of the 2012 ADIA Research Grant. The $7,500 grant is bestowed by the Australian Dental Research Foundation (ADRF) on an annual basis using funds donated by ADIA.
In his grant application, Prof. Zoellner said that the purpose of his research project is to examine
increased diversity amongst cancer cells by cellular sipping from fibroblasts
The grant application notes that
in an earlier study, it was shown that when osteosarcoma cells contact vessel endothelium, the cancer cells cause apoptotic endothelial death, opposing a separate proliferative-angiogenic effect mediated by soluble cancer cell factors. For the current research project, experiments were repeated with fibroblasts instead of endothelium, with a similar apoptotic response expected to account for tissue replacement by invading cancer. However, the data unveiled a new and surprising aspect of cancer cell biology – ‘cellular sipping’.
Initially, fibroblasts were co-cultured with osteosarcoma cells, using a membrane cancer cell marker to distinguish the two cell types. Here, the unlabelled fibroblasts appeared to reduce in number, consistent with the expectation of fibroblast apoptosis. However, no evidence for apoptosis was ever found. Instead, it was observed that fibroblasts were not dying, but were simply picking up cancer cell membrane markers. Fluorescent markers to label membrane, cytoplasm and nuclei of both fibroblasts and a range of different cancer cell lines, confirmed extensive exchange of membrane and cytoplasm between cancer cells and fibroblasts via cell processes – a mechanism that we termed ‘cellular sipping’ to illustrate the manner in which cancer cells sample contents from fibroblasts.
It was further demonstrated that there was changed cancer cell behaviour after imbibing fibroblast material, as evidenced by altered cancer cell morphology, while there was also altered fibroblast cytokine synthesis.
It is widely accepted that immune and chemotherapy evasion by cancer cells involves out-growth of genetically mutated resistant cancer sub-clones. However, our discovery reveals that even within sub-clones of cancer cells, there can be almost infinite cancer cell diversity due to cellular sipping. This helps account for both immune evasion and cancer therapy resistance, but raises hope for better treatment outcomes if cellular sipping can be blocked.
There is now a need to properly characterise the precise nature and mechanism of cellular sipping, with a view to exploiting this new insight into cancer biology for improved cancer treatment.
The ADIA Chief Executive Officer, Troy Williams, said that the dental industry was pleased to support research into this area and funding of this grant application was consistent with the Association's stated aim of to advancing the oral health care of all Australians.
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