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A Comparative Study of Oncolytic Vaccinia Viruses Harboring Different Marine Lectins in Breast Cancer Cells
Yanrong Zhou1, Qianpeng Wang1, Qi Ying1
1College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China.
Abstract:
Our previous studies demonstrated that arming vaccinia viruses with marine lectins enhanced the antitumor efficacy in several cancer cells. This study aims to compare the efficacy of oncolytic vaccinia viruses harboring Tachypleus tridentatus lectin (oncoVV-TTL), Aphrocallistes vastus lectin (oncoVV-AVL), white-spotted charr lectin (oncoVV-WCL), and Asterina pectinifera lectin (oncoVV-APL) in breast cancer cells (BC). These results indicated that oncoVV-AVL elicited the highest anti-tumor effect, followed by oncoVV-APL, while oncoVV-TTL and oncoVV-WCL had lower effects in BC. Further studies showed that apoptosis and replication may work together to enhance the cytotoxicity of oncoVV-lectins in a cell-type dependent manner. TTL/AVL/APL/WCL may mediate multiple pathways, including ERK, JNK, Hippo, and PI3K pathways, to promote oncoVV replication in MDA-MB-231 cells. In contrast, these pathways did not affect oncoVV-TTL/AVL/APL/WCL replication in MCF-7 cells, suggesting that the mechanisms of recombinant viruses in MCF-7 (ER+, PR+) and MDA-MB-231 (TNBC) cells were significantly different. Based on this study, we hypothesized that ER or PR may be responsible for the differences in promoting viral replication and inducing apoptosis between MCF-7 and MDA-MB-231 cells, but the specific mechanism needs to be further explored. In addition, small-molecule drugs targeting key cellular signaling pathways, including MAPK, PI3K/Akt, and Hippo, could be conjunction with oncoVV-AVL to promote breast cancer therapy, and key pathway factors in the JNK and PI3K pathways may be related to the efficacy of oncoVV-APL/TTL/WCL. This study provides a basis for applying oncolytic vaccinia virus in breast carcinoma.
Insights
Oncolytic vaccinia viruses armed with marine lectins show potential for breast cancer therapy. Aphrocallistes vastus lectin (oncoVV-AVL) demonstrated the strongest anti-tumor effect, working through distinct cellular pathways in different breast cancer types.
Area of Science:
- Oncolytic virotherapy
- Cancer immunology
- Molecular oncology
Background:
- Previous studies showed marine lectin-armed vaccinia viruses enhance antitumor efficacy.
- Marine lectins offer a novel strategy for augmenting oncolytic vaccinia virus (oncoVV) activity.
- Understanding lectin-specific mechanisms in breast cancer is crucial for therapeutic development.
Purpose of the Study:
- To compare the efficacy of four oncolytic vaccinia viruses armed with different marine lectins (Tachypleus tridentatus lectin, Aphrocallistes vastus lectin, white-spotted charr lectin, Asterina pectinifera lectin) in breast cancer cells.
- To investigate the cellular mechanisms, including apoptosis and viral replication pathways, underlying the oncoVV-lectin activity in distinct breast cancer subtypes.
- To explore potential combination therapies involving oncoVV-lectins and small-molecule drugs.
Main Methods:
- Engineered oncolytic vaccinia viruses (oncoVV) harboring specific marine lectins: oncoVV-TTL, oncoVV-AVL, oncoVV-WCL, and oncoVV-APL.
- Assessed antitumor efficacy in breast cancer (BC) cell lines, including MDA-MB-231 (TNBC) and MCF-7 (ER+, PR+).
- Investigated cellular pathways (ERK, JNK, Hippo, PI3K) involved in viral replication and apoptosis induction.
Main Results:
- OncoVV-AVL exhibited the highest antitumor effect in breast cancer cells, followed by oncoVV-APL. OncoVV-TTL and oncoVV-WCL showed lower efficacy.
- Apoptosis and viral replication synergistically enhanced oncoVV-lectin cytotoxicity in a cell-type-dependent manner.
- Distinct signaling pathway involvement (ERK, JNK, Hippo, PI3K) in viral replication was observed between MDA-MB-231 and MCF-7 cells, suggesting ER/PR roles.
Conclusions:
- Oncolytic vaccinia viruses armed with marine lectins, particularly oncoVV-AVL, represent a promising strategy for breast cancer therapy.
- The efficacy and mechanisms of oncoVV-lectins are significantly influenced by breast cancer cell type, involving differential activation of cellular signaling pathways.
- Combination therapy with oncoVV-AVL and targeted small-molecule drugs (MAPK, PI3K/Akt, Hippo inhibitors) warrants further investigation for enhanced breast cancer treatment.
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