The role of microvesicles in cancer and viral infection

Jorfi, Samireh (2012) The role of microvesicles in cancer and viral infection. Doctoral thesis, London Metropolitan University.

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Abstract / Description

Microvesicles are shed constitutively, or upon activation from both normal and malignant cells. Although recent studies have reported various nonlytic virus release mechanisms, this mode of virus transmission to secondary sites of infection has remained unclear. This study identified that Coxsackie virus B1 (CVB1) entry into HeLa cells results in apoptosis and production of virus-induced apoptotic microvesicles (vaMVs) by infected cells. Flow cytometery and fluorescence microscopy data illustrated that these vaMVs carry and disseminate CVB1 virions to new host cells via a non lytic MV-to-cell viral mechanism. Inhibition of MV production by siRNA knockdown of CAPNS1 in HeLa cells suggested that these vesicles mediate the spread of apoptosis to secondary sites of infection and the vaMVs could mediate non lytic MV-to-cell transmission. This thesis also identified a new mechanism for multi-drug resistance involving the efflux of anticancer drugs from cancer cells mediated by release of microvesicles, removing the drug from treated cancer cells. Immunoblotting and flow cytometery data showed that transcriptional silencing of calpain by siRNA knockdown of CAPNS1 in PC3M cells prior to drug treatment inhibits MV release and results in induced apoptosis in cells. This mechanism contributes to understanding the reasons for insensitivity to drug-induced apoptosis and the induction of drug-detoxification by cancer cells. This study has yielded important information about how to circumvent drug resistance to improve cancer chemotherapy. Furthermore, fluorescence microscopy results postulate that induction of MV release with agonist agents and anticancer drugs, results in damage to the host plasma membrane, which must be resealed immediately using activated Iysosomes if the host cell is to survive and proliferate.

Item Type:	Thesis (Doctoral)
Additional Information:	uk.bl.ethos.590129
Uncontrolled Keywords:	virus-induced apoptotic microvesicles (vaMVs); virus transmission; Coxsackie virus B1 (CVB1); cancer cells; HeLa cells; apoptosis
Subjects:	600 Technology > 610 Medicine & health
Department:	School of Human Sciences
Depositing User:	Chiara Repetto
Date Deposited:	25 Apr 2022 10:42
Last Modified:	25 Apr 2022 10:42
URI:	https://repository.londonmet.ac.uk/id/eprint/7489

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