Researchers at the University of Maryland 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 (1). Targeting these microtentacles might prove to be a new way to prevent or slow the growth of these secondary cancers, scientists say. The researchers used Roches's (SIX: RO, ROG; OTCQX: RHHBY) 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.
The cytoskeletal organization of detached and circulating tumor cells (CTCs) is currently not well defined and may provide potential targets for new therapies to limit metastatic tumor spread. CTCs reattach in vivo in distant tissues by a mechanism that is tubulindependent and suppressed by polymerized actin. The cytoskeletal mechanisms that promote reattachment of CTCs match exactly with the mechanisms supporting tubulin microtentacles (McTN), which the researchers have recently identified in detached breast tumor cells. The new study aimed to investigate how McTN formation is affected by the microtubuleassociated protein, tau, which is expressed in a subset of chemotherapyresistant breast cancers. The results show that endogenous tau protein localizes to McTNs and is both necessary and sufficient to promote McTN extension in detached breast tumor cells. Tauinduced McTNs increase reattachment of suspended cells and retention of CTCs in lung capillaries. Analysis of individualmatched primary and metastatic tumors reveals that 52% possess tauexpression in metastases and 26% display significantly increased tauexpression over disease progression. Tauenrichment in metastatic tumors and the ability of tau to promote tumor cell reattachment through McTN formation support a model in which tauinduced microtubule stabilization provides a selective advantage during tumor metastasis.
"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. Drugs that reduce tau expression may hold potential to inhibit tumor metastasis," says 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.
(1) Oncogene advance online publication, 15 March 2010; doi:10.1038/onc.2010.68
The cytoskeletal organization of detached and circulating tumor cells (CTCs) is currently not well defined and may provide potential targets for new therapies to limit metastatic tumor spread. CTCs reattach in vivo in distant tissues by a mechanism that is tubulindependent and suppressed by polymerized actin. The cytoskeletal mechanisms that promote reattachment of CTCs match exactly with the mechanisms supporting tubulin microtentacles (McTN), which the researchers have recently identified in detached breast tumor cells. The new study aimed to investigate how McTN formation is affected by the microtubuleassociated protein, tau, which is expressed in a subset of chemotherapyresistant breast cancers. The results show that endogenous tau protein localizes to McTNs and is both necessary and sufficient to promote McTN extension in detached breast tumor cells. Tauinduced McTNs increase reattachment of suspended cells and retention of CTCs in lung capillaries. Analysis of individualmatched primary and metastatic tumors reveals that 52% possess tauexpression in metastases and 26% display significantly increased tauexpression over disease progression. Tauenrichment in metastatic tumors and the ability of tau to promote tumor cell reattachment through McTN formation support a model in which tauinduced microtubule stabilization provides a selective advantage during tumor metastasis.
"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. Drugs that reduce tau expression may hold potential to inhibit tumor metastasis," says 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.
(1) Oncogene advance online publication, 15 March 2010; doi:10.1038/onc.2010.68
