Inhibition of Metastatic Tumor Growth and Metastasis via Targeting Metastatic Breast Cancer by Chlorotoxin-Modified Liposomes

2014 ◽  
Vol 11 (10) ◽  
pp. 3233-3241 ◽  
Author(s):  
Chao Qin ◽  
Bing He ◽  
Wenbing Dai ◽  
Hua Zhang ◽  
Xueqing Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Growth ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Tumor Growth And Metastasis

scholarly journals cPLA2 Blockade Attenuates S100A7-Mediated Breast Tumorigenicity by Inhibiting the Immunosuppressive Tumor Microenvironment

2021 ◽  
Author(s):  
SANJAY MISHRA ◽  
Manish Charan ◽  
Rajni Kant Shukla ◽  
Pranay Agarwal ◽  
Swati Misri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Immunosuppressive Tumor Microenvironment ◽  
Tumor Growth And Metastasis ◽  
Breast Cancer Growth

Abstract Background: Metastasis is the major cause of mortality in breast cancer; however, the molecular mechanisms remain elusive. In our previous study, we demonstrated that S100A7/RAGE mediates breast cancer growth and metastasis by recruitment of tumor-associated macrophages. However, the downstream S100A7-mediated inflammatory oncogenic signaling cascade that enhances breast tumor growth and metastasis by generating the immunosuppressive tumor microenvironment (iTME) has not been studied. In this present study, we aimed to investigate the S100A7 and cPLA2 cross-talk in enhancing tumor growth and metastasis through enhancing the iTME.Methods: Human breast cancer tissue and plasma samples were used to analyze the expression of S100A7, cPLA2, and PGE2 titer. S100A7-overexpressing or downregulated human metastatic breast cancer cells were used to evaluate the S100A7-mediated downstream signaling mechanisms. Bi-transgenic mS100a7a15 overexpression, TNBC C3(1)/Tag transgenic, and humanized patient-derived xenograft mouse models and cPLA2 inhibitor (AACOCF3) were used to investigate the role of S100A7/cPLA2/PGE2 signaling in tumor growth and metastasis. Additionally, CODEX, a highly advanced multiplexed imaging was employed to delineate the effect of S100A7/cPLA2 inhibition on the recruitment of various immune cells.Results: S100A7 and cPLA2 are highly expressed and positively correlated in malignant breast cancer patients. S100A7/RAGE upregulates cPLA2/PGE2 axis in aggressive breast cancer cells. Furthermore, S100A7 is positively correlated with PGE2 in breast cancer patients. Moreover, cPLA2 pharmacological inhibition suppressed S100A7-mediated tumor growth and metastasis in multiple pre-clinical models. Mechanistically, S100A7-mediated activation of cPLA2 enhances the recruitment of immunosuppressive myeloid cells by increasing PGE2 to fuel breast cancer growth and its secondary spread. We revealed that cPLA2 inhibitor mitigates S100A7-mediated breast tumorigenicity by suppressing the iTME. Furthermore, CODEX imaging data showed that cPLA2 inhibition increased the infiltration of CD4+/CD8+ T cells in the TME. Analysis of metastatic breast cancer samples revealed a positive correlation between S100A7/cPLA2 with CD163+ tumor-associated M2-macrophages.Conclusions: Our study shows that cross-talk between S100A7 and cPLA2 plays an important role in enhancing breast tumor growth and metastasis by generating an immunosuppressive tumor microenvironment and reducing infiltration of T cells. Furthermore, S100A7 could be used as a novel non-invasive prognostic marker and cPLA2 inhibitors as promising drugs against S100A7-overexpressing metastatic breast cancer.

Rab11 family-interacting protein 4, RAB11FIP4, is a differentially expressed gene in brain metastatic human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Differentially Expressed Gene ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Interacting Protein ◽  
Primary Tumors ◽  
Free Survival ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that Rab11 family-interacting protein 4, encoded by RAB11FIP4, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. RAB11FIP4 mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of RAB11FIP4 in primary tumors was significantly correlated with patient recurrence-free survival and distant metastasis-free survival. Modulation of RAB11FIP4 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.

scholarly journals TOM1L2 is a differentially expressed gene in human metastatic breast cancer, in the brain and in the lymph nodes.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Nodes ◽  
Differentially Expressed Gene ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Primary Tumors ◽  
Node Metastases ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that the target of myb1-like 2, encoded by TOM1L2, was among the genes whose expression was most different in the brain and lymph node metastases of patients with metastatic breast cancer. TOM1L2 mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of TOM1L2 in primary tumors was significantly correlated with patient overall survival in patients with breast cancer. Modulation of TOM1L2 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain while evading immune clearance in the lymph nodes in humans with metastatic breast cancer.

scholarly journals The gastrin releasing peptide, GRP, is differentially expressed in brain metastatic breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
Microarray Data ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Primary Tumors ◽  
Gastrin Releasing Peptide ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes to discover genes associated with brain metastasis in patients with metastatic breast cancer. We found that the gastrin releasing peptide, encoded by GRP, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Molecular functions of gastrin releasing peptide may be relevant to the processes by which tumor cells of the breast metastasize to the breast. Down-regulation of GRP may be an important event for metastasis of primary tumor-derived cancer cells to the brain in humans with metastatic breast cancer.

scholarly journals Versican (VCAN) is differentially expressed in metastatic breast cancer, both in metastases to the brain and to the lymph nodes.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Nodes ◽  
Microarray Data ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Primary Tumors ◽  
Tumor Tissues ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes to discover genes associated with brain metastasis in patients with metastatic breast cancer. We found that the chondroitin sulfate proteoglycan versican, encoded by VCAN, was among the genes whose expression was most different in the metastatic tumor tissues of patients with metastatic breast cancer, both in metastases to brain and to the lymph nodes when compared to primary tumors of the breast. Molecular functions (6-9) and down-regulation of VCAN may be important for metastasis of primary tumor-derived cancer cells to the lymph nodes and to the brain in humans with metastatic breast cancer, and suggests some level of common origin for metastases that reside in the lymph nodes and colonize the brain.

scholarly journals ASNSD1 is differentially expressed in brain metastatic human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Human Breast Cancer ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Asparagine Synthetase ◽  
Human Breast ◽  
Primary Tumors ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that asparagine synthetase domain containing 1, encoded by ASNSD1, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. ASNSD1 mRNA was present at decreased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of ASNSD1 in primary tumors was significantly correlated with patient post-progression survival. Modulation of ASNSD1 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.

scholarly journals FGF12 is differentially expressed in the brain metastases of patients with metastatic breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastases ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Normal Breast ◽  
Primary Tumors ◽  
Breast Tissues ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes to discover genes associated with brain metastasis in patients with metastatic breast cancer. We found that the fibroblast growth factor 12, encoded by FGF12, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to normal breast tissues. FGF12 mRNA expression was significantly higher in brain metastatic tissues as compared to primary tumors of the breast. Up-regulation of FGF12 expression may contribute to metastasis of tumor cells from the breast to the brain in humans with metastatic breast cancer.

scholarly journals C1R is differentially expressed in the brain metastases of patients with metastatic breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastases ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Normal Breast ◽  
Primary Tumors ◽  
Breast Tissues ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes to discover genes associated with brain metastasis in patients with metastatic breast cancer. We found that the complement component 1, r subcomponent, encoded by C1R, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to normal breast tissues. C1R mRNA was present at significantly reduced quantities in brain metastatic tissues as compared to primary tumors of the breast. Down-regulation of C1R expression may contribute to metastasis of tumor cells from the breast to the brain in humans with metastatic breast cancer.

scholarly journals NECAB3 is a differentially expressed gene in human metastatic breast cancer, in the brain and in the lymph nodes.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Nodes ◽  
Calcium Binding ◽  
Differentially Expressed Gene ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Primary Tumors ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that N-terminal EF-hand calcium-binding protein 3, encoded by NECAB3, was among the genes whose expression was most different in the brain and lymph node metastases of patients with metastatic breast cancer. NECAB3 mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of NECAB3 in primary tumors was significantly correlated with patient recurrence-free survival in patients with breast cancer. Modulation of NECAB3 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain while evading immune clearance in the lymph nodes in humans with metastatic breast cancer.

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