scholarly journals Stromal platelet-derived growth factor receptor-β signaling promotes breast cancer metastasis in the brain

2020 ◽  
pp. canres.3731.2019 ◽  
Author(s):  
Katie A. Thies ◽  
Anisha M. Hammer ◽  
Blake E. Hildreth ◽  
Sarah A. Steck ◽  
Jonathan M. Spehar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Cancer Metastasis ◽  
Growth Factor Receptor ◽  
Breast Cancer Metastasis ◽  
Platelet Derived Growth Factor ◽  
The Brain

scholarly journals BSCI-11. STROMAL PLATELET DERIVED GROWTH FACTOR RECEPTOR-β (PDGFRβ) PROMOTES BREAST CANCER BRAIN METASTASIS

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i3-i3
Author(s):  
Katie Thies ◽  
Anisha Hammer ◽  
Blake Hildreth ◽  
Luke Russell ◽  
Steven Sizemore ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Tumor Cells ◽  
Mammary Tumor ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Mammary Tumor Cells ◽  
The Brain

Abstract Stromal platelet-derived growth factor receptor-beta (PDGFRβ) has emerged as an actionable mediator of breast tumor-stromal communication. As a receptor tyrosine kinase, PDGFRβ is activated by its ligand, PDGFB, which is released by neighboring tumor epithelium and endothelium. However, how PDGF signaling mediates breast cancer (BC) initiation, progression, and metastasis remains unclear. To evaluate PDGFRβ in this disease, we developed a mouse model of stromal-specific PDGFRβ activation using the Fsp-cre transgene previously published by our group. Mesenchymal-specific activation of PDGFRβ promotes preferential experimental brain metastasis of PDGFB-expressing mammary tumor cells when injected intravenously and accelerates intracranial tumor growth of these cells. Mammary tumor cells expressing low levels of PDGFB do not exhibit a similar increase in brain metastases in PDGFRβ mutant mice. To our knowledge, this is the first example where genetic manipulation of the stroma leads to an increased incidence of BCBM. Our pre-clinical data suggests that primary breast tumors that express high PDGFB could preferentially metastasize to the brain. To test this in patients, we analyzed PDGFB protein expression in a tissue microarray comprised of HER2-positive and triple negative BC primary tumors. While high PDGFB did not correlate with site-independent metastatic recurrence, it was prognostic of brain metastasis, mirroring our mouse data. Our findings suggest that high primary tumor PDGFB expression defines a subset of BC patients predisposed to brain metastases. These patients may benefit from therapeutic intervention of PDGFRβ signaling. To test this pre-clinically, we treated mice harboring intracranial tumors with the PDGFR-specific inhibitor, crenolanib. Excitingly, crenolanib treatment significantly inhibited the brain tumor burden in these mice. Combined, our findings (1) advocate that primary tumor expression of PDGFB is a novel prognostic biomarker for the development of BCBM and (2) support clinical trial evaluation of PDGFR inhibitors for the prevention and treatment of BCBM.

KISS1/KISS1R and Breast Cancer: Metastasis Promoter

2019 ◽  
Vol 37 (04) ◽  
pp. 197-206 ◽  
Author(s):  
Stephania Guzman ◽  
Muriel Brackstone ◽  
Frederic Wondisford ◽  
Andy V. Babwah ◽  
Moshmi Bhattacharya
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Growth Factor ◽  
Cancer Metastasis ◽  
Transforming Growth Factor ◽  
Growth Factor Receptor ◽  
Transforming Growth Factor Β ◽  
Suppressor Gene ◽  
Breast Cancer Metastasis ◽  
Metastasis Suppressor

AbstractKisspeptins (KPs), peptide products of the kisspeptin-1 (KISS1) gene, are the endogenous ligands for the KISS1 receptor, KISS1R, which is a G protein-coupled receptor. In many human tumors, KISS1 functions as a metastasis-suppressor gene and KISS1/KISS1R signaling has antimetastatic and tumor-suppressor roles. On the contrary, emerging evidence indicates that the KP/KISS1R pathway plays detrimental roles in triple negative breast cancer (TNBC), the most difficult type of breast cancer to treat. TNBC patients initially respond to chemotherapy, but tumors acquire drug resistance and many patients relapse and die of metastases within a few years. In this review, we summarize recent developments in the understanding of the mechanisms by which KP/KISS1R signaling plays an adverse role in TNBC. This includes focusing on how KISS1R signaling regulates the cell cytoskeleton to induce tumor invadopodia formation and how KISS1R communicates with growth factor receptors such as the epidermal growth factor receptor, the receptor tyrosine kinase AXL, and transforming growth factor-β to promote cell invasion, metastasis, and drug resistance.

Sex steroids and breast cancer metastasis

2010 ◽  
Vol 3 (2) ◽  
Author(s):  
Xiao-Dong Fu ◽  
Eleonora Russo ◽  
Sara Zullino ◽  
Andrea R. Genazzani ◽  
Tommaso Simoncini
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Sex Steroids ◽  
Cancer Metastasis ◽  
Growth Factor Receptor ◽  
Breast Cancer Metastasis ◽  
Tissue Growth ◽  
Actin Binding

AbstractSex steroids, particularly estrogen and progesterone, promote normal breast tissue growth and differentiation. Prolonged exposure of estrogen and/or progesterone is considered a risk factor for breast cancer carcinogenesis, and the effects of sex steroids on breast cancer metastasis are controversial. Emerging evidence indicates that sex steroids regulate breast cancer metastatic processes via nongenomic and genomic mechanisms. Through the regulation of actin-binding proteins estrogen and progesterone rapidly provoke actin cytoskeleton reorganization in breast cancer cells, leading to formation of membrane structures facilitating breast cancer cell migration and invasion. In addition, steroid receptors interact and trans-activate receptor tyrosine kinases (including epidermal growth factor receptor and insulin-like growth factor receptor), resulting in growth factor-like effects that promote cancer cell invasive behavior. Moreover, sex steroids regulate the expression of metastasis-associated molecules, such as E-cadherin, matrix metalloproteinases, growth factors, chemokines and their receptors, leading to epithelial-to-mesenchymal-like transition. However, there is also evidence that sex steroids and their receptors protect against breast cancer cell invasiveness through distinct mechanisms. Here, we present an overview of the currently identified actions of sex steroids on breast cancer metastasis and their potential clinical implications.

Role of the CXCR4/CXCL12 signaling axis in breast cancer metastasis to the brain

2008 ◽  
Vol 27 (2) ◽  
pp. 97-105 ◽  
Author(s):  
Cimona V. Hinton ◽  
Shalom Avraham ◽  
Hava Karsenty Avraham
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Signaling Axis ◽  
The Brain

scholarly journals The placental growth factor (PGF) is differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Placental Growth Factor ◽  
Differentially Expressed ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Epidermal Growth ◽  
The Brain

Trastuzumab, a monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2) is utilized for the treatment of human breast cancer (1, 2), but a complete understanding of how tumor signal transduction is modulated by trastuzumab treatment is lacking. By mining published and public microarray and gene expression data (3, 4) from the primary tumors of patients treated with trastuzumab, we found that the placental growth factor, encoded by PGF was among the genes most differentially expressed in the primary tumors of patients treated with trastuzumab, and expressed at lower levels in the tumors of patients treated with trastuzumab. Thus, the use of trastuzumab in patients with breast cancer is associated with increased expression of a growth factor that is chemotactic, angiogenic (5) and important for growth of blood vessels in the brain (6).

TAMI-05. FATTY ACID SYNTHESIS IS REQUIRED FOR HER2+ BREAST CANCER BRAIN METASTASIS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi199-vi199
Author(s):  
Gino Ferraro ◽  
Ahmed Ali ◽  
Alba Luengo ◽  
Amy Deik ◽  
Keene Abbott ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Fatty Acid ◽  
Growth Factor ◽  
Fatty Acid Synthesis ◽  
Growth Factor Receptor ◽  
Breast Tumors ◽  
Acid Synthesis ◽  
Epidermal Growth ◽  
The Brain

Abstract Brain metastases are refractory to therapies that control systemic disease in patients with human epidermal growth factor receptor 2-positive breast cancer and the brain microenvironment contributes to this therapy resistance. Nutrient availability can vary across tissues, therefore metabolic adaptations required for brain metastatic breast cancer growth may introduce liabilities that can be exploited for therapy. Here we assessed how metabolism differs between breast tumors in brain versus extracranial sites and found that fatty acid synthesis is elevated in breast tumors growing in the brain. We determine that this phenotype is an adaptation to decreased lipid availability in the brain relative to other tissues, resulting in site-specific dependency on fatty acid synthesis for breast tumors growing at this site. Genetic or pharmacological inhibition of fatty acid synthase reduces human epidermal growth factor receptor 2-positive breast tumor growth in the brain, demonstrating that differences in nutrient availability across metastatic sites can result in targetable metabolic dependencies.

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