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Researchers study ‘microtentacles’ on breast tumour cells

Researchers at the Marlene and Stewart Greenebaum Cancer Center have studied the involvement of ‘microtentacles’, or extensions of the plasma membrane of breast cancer cells, in how cancers spread to distant locations in the body.

Targeting these microtentacles might prove to be a new way to prevent or slow the growth of these secondary cancers. The cytoskeletal organization of detached and circulating tumour cells (CTCs) is currently not well defined and might provide potential targets for new therapies to limit metastatic tumour spread.

CTCs reattach in vivo in distant tissues by a mechanism that is tubulin dependent and suppressed by polymerized actin. The cytoskeletal mechanisms that promote reattachment of CTCs match exactly with the mechanisms supporting tubulin microtentacles, which the researchers have recently identified in detached breast tumour cells.

The new study aimed to investigate how microtentacle formation is affected by the microtubule-associated protein, tau, which is expressed in a subset of chemotherapy-resistant breast cancers. The results show that endogenous tau protein localizes to microtentacles and is both necessary and sufficient to promote microtentacle extension in detached breast tumour cells.

Tau-induced microtentacles increase reattachment of suspended cells and retention of CTCs in lung capillaries. Analysis of individual-matched primary and metastatic tumours reveals that 52% possess tau expression in metastases, and 26% display significantly increased tau expression over disease progression.

Tau enrichment in metastatic tumours and the ability of tau to promote tumour cell reattachment through microtentacle formation support a model in which tau-induced microtubule stabilization provides a selective advantage during tumour metastasis. The researchers used Roches’s xCELLigence RTCA SP Instrument to measure attachment as the relative impedance change, cell index, across the microelectronic sensors at the bottom of the system´s E-Plates.

‘We hope that through our research, we will be able to identify drugs that will target the growth of these microtentacles and help to stop the spread of the original cancer,’ said the senior author, Stuart S. Martin, PhD, a researcher at the University of Maryland Greenebaum Cancer Center and associate professor of physiology at the University of Maryland School of Medicine. ‘Drugs that reduce tau expression may hold potential to inhibit tumour metastasis.’

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