Identification of two cancer stem cell-like populations in triple-negative breast cancer xenografts

Nakayama, Jun; Matsunaga, Hiroko; Arikawa, Koji; Yoda, Takuya; Hosokawa, Masahito; Takeyama, Haruko; Yamamoto, Yusuke; Semba, Kentaro

doi:10.1242/dmm.049538

Cited by 8 publications

(6 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Figures 10C and 10D display representative images of metastatic tumors in the liver. The MDA-MB-231 tumor used in the xenograft model is well-known to metastasize to various organs, including the liver, lymph nodes, lungs, bones, and brain [36]. Although the nanoparticle formulation inhibited cell migration in vitro, a similar effect was not observed in vivo at the current dose.…”

Section: Discussionmentioning

confidence: 86%

Evaluation of mAb 2C5-modified dendrimer-based micelles for the co-delivery of siRNA and chemotherapeutic drug in xenograft mice model

Yalamarty,

Filipczak,

Pathrikar

et al. 2023

Preprint

View full text Add to dashboard Cite

A combination therapy with small interfering RNA (siRNA) and chemotherapeutic drug is proven to be effective in downregulating the cancer resistance proteins, such as P-glycoprotein (P-gp). These proteins are involved in multidrug resistance (MDR) of tumors. MDR lowers the efficacy of chemotherapy and even renders it ineffective. A possible strategy to counteract the resistance is by downregulating the resistance proteins using siRNA. A targeted formulation capable of delivering siRNA and chemotherapeutic drug will not only downregulate P-gp but also increase the concentration of the chemotherapeutic drug at the site of tumor thereby increasing the therapeutic effect and lowering the systemic exposure. In this study, monoclonal antibody 2C5-modified dendrimer-based micelles were used to co-deliver siRNA and doxorubicin (DOX) to the tumor site in both male and female xenograft mice model. The nucleosome-specific 2C5 antibody recognizes the cancer cells via the cell-surface bound nucleosomes. The ability of the 2C5-modified formulation in affecting the metastasis of highly aggressive triple negative breast cancer (MDA-MB-231) was assessed via wound healing assay where the 2C5-modified formulation halved the rate at which the cells were migrating. Further, the therapeutic efficacy of the formulation was assessed by measuring the tumor volume progression where the 2C5-modified nanoparticle group had a similar tumor volume to the free drug group at the end of the study, although a 50% increase in DOX concentrations in blood was observed after the last dose of nanoparticle. Despite a higher DOX concentration and residence time we did not observe any systemic toxicities in the nanoparticle groups. The free drug group on the other hand showed body weight reduction as well as the visible irritation around the injection spot. The treatment group with 2C5-modified micelles has shown to be safe at the current dose of DOX and siRNA.The ability of 2C5 antibody-functionalized nanoparticles in delivering cargo to the tumor site in vivo was evaluated for DOX using ex vivo imaging and siRNA by western blot study to evaluate the levels of P-gp. Furthermore, the siRNA mediated P-gp downregualtion was studied using western blotting assay. We observed a 29% reduction of P-gp levels in both males and females with respect to the control (BHG). We also conclude that the dose of DOX and siRNA should be further optimized to have a better efficacy in a metastatic tumor model, which will be the subject of our future studies.

show abstract

Section: Discussionmentioning

confidence: 86%

Evaluation of mAb 2C5-modified dendrimer-based micelles for the co-delivery of siRNA and chemotherapeutic drug in xenograft mice model

Yalamarty,

Filipczak,

Pathrikar

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…[ 22 , 23 ] Silencing HMGA1 can block the metastasis of breast cancer and colorectal cancer and reduce the proportion of tumor stem cells. [ 24 – 26 ] As reported in a recent study, the high expression of HMGA1 may be induced by the secretion of breast cancer cells, and signals may be sent through the advanced glycation end-products receptor, which would promote invasiveness. [ 26 ] In addition, previous studies demonstrated that the overexpression of HMGA1 can regulate the epigenetic silencing of genes related to tumor progression.…”

Section: Discussionmentioning

confidence: 99%

Association between HMGA1 and immunosuppression in hepatocellular carcinoma: A comprehensive bioinformatics analysis

et al. 2023

View full text Add to dashboard Cite

The high mobility group A1 (HMGA1) gene is overexpressed in malignant tumors, and its expression level correlates with the progression and metastasis of tumors. However, the specific role of HMGA1 in hepatocellular carcinoma (HCC) and relevant influencing approaches in tumor immunity remain unclear. In this study, the expression and clinical significance of HMGA1 in HCC immunity were analyzed. The expression levels of HMGA1 mRNA and protein in HCC tissue and normal liver tissue were analyzed based on the cancer genome atlas, the gene expression omnibus and the Human Protein Atlas databases. The correlation between HMGA1 and clinicopathological factors was analyzed, and survival was estimated based on the expression of HMGA1. Gene set cancer analysis and the TISIDB database were used to identify tumor-infiltrating immune cells and immune inhibitors. Gene set enrichment analysis was performed to determine the involved signaling pathway. The HMGA1 genetic alterations were identified with the cBioPortal for Cancer Genomics. The expression of HMGA1 mRNA and protein was significantly higher in HCC tissue and negatively correlated with survival. Neutrophils, Th17 cells, several immune inhibitors, and signaling pathways were positively correlated with the expression of HMGA1. Amplification was the main type of genetic alteration in HMGA1. These findings demonstrate that HMGA1 can be a therapeutic target and a potential biomarker to predict the prognosis of patients with HCC. HMGA1 may affect the progression of HCC by suppressing the immune function of these patients.

show abstract

“…A total of 1.0 × 10 6 NMuMG‐luc‐HOXB7 cells, NMuMG‐luc‐HOXB7‐shGFP cells, or NMuMG‐luc‐HOXB7‐shSTAT3#3 cells were transplanted into fourth fat pads of 6‐weeks‐old BALB/cSlc‐nu/nu female mice as previously described (Nakayama et al, 2017, 2022). After the injection, the transplantation sites were palpated for every 2–3 days to measure tumor formation time and mice were monitored primary tumor formation and metastasis formation by in vivo imaging system (IVIS Lumina Xr3; Perkin‐Elmer, Waltham, MA) for every week.…”

Section: Methodsmentioning

confidence: 99%

HOXB7 induces STAT3‐mediated transformation and lung metastasis in immortalized mammary gland NMuMG cells

et al. 2023

Self Cite

View full text Add to dashboard Cite

The homeobox family genes are often dysregulated in various cancer types.Particularly HOXB7 amplification and overexpression correlate with poor prognosis in various cancer such as gastric, pancreatic, and lung cancers. Moreover, HOXB7 is known to contribute to cancer progression by promoting epithelial to mesenchymal transition, anticancer drug resistance, and angiogenesis. In this study, we show that HOXB7 is coamplified with ERBB2 in a subset of breast cancer patients and HOXB7 expression correlates with poor prognosis in HER2-positive breast cancer patients. This clinical observation is supported by the following results-HOXB7 overexpression in an immortalized murine mammary gland epithelial cell line NMuMG induces cellular transformation in vitro, tumorigenesis, and lung metastasis through the activation of JAK-STAT signaling.

show abstract

Identification of two cancer stem cell-like populations in triple-negative breast cancer xenografts

Cited by 8 publications

References 48 publications

Evaluation of mAb 2C5-modified dendrimer-based micelles for the co-delivery of siRNA and chemotherapeutic drug in xenograft mice model

Evaluation of mAb 2C5-modified dendrimer-based micelles for the co-delivery of siRNA and chemotherapeutic drug in xenograft mice model

Association between HMGA1 and immunosuppression in hepatocellular carcinoma: A comprehensive bioinformatics analysis

HOXB7 induces STAT3‐mediated transformation and lung metastasis in immortalized mammary gland NMuMG cells

Contact Info

Product

Resources

About