scholarly journals Detection of PIK3CA Mutations in Breast Cancer Bone Metastases

ISRN Oncology ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-8
Author(s):  
Manijeh Daneshmand ◽  
Jennifer E. L. Hanson ◽  
Mitra Nabavi ◽  
John F. Hilton ◽  
Lisa Vandermeer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Bone Metastases ◽  
Cancer Cells ◽  
Primary Tumour ◽  
Breast Cancer Patients ◽  
Ct Guided ◽  
Mutation Status ◽  
Bone Biopsies ◽  
Metastatic Sites

Background. An important goal of personalized cancer therapy is to tailor specific therapies to the mutational profile of individual patients. However, whole genome sequencing studies have shown that the mutational profiles of cancers evolve over time and often differ between primary and metastatic sites. Activating point mutations in the PIK3CA gene are common in primary breast cancer tumors, but their presence in breast cancer bone metastases has not been assessed previously. Results. Fourteen patients with breast cancer bone metastases were biopsied by three methods: CT-guided bone biopsies; bone marrow trephine biopsies; and bone marrow aspiration. Samples that were positive for cancer cells were obtained from six patients. Three of these patients had detectable PIK3CA mutations in bone marrow cancer cells. Primary tumor samples were available for four of the six patients assessed for PIK3CA status in their bone metastases. For each of these, the PIK3CA mutation status was the same in the primary and metastatic sites. Conclusions. PIK3CA mutations occur frequently in breast cancer bone metastases. The PIK3CA mutation status in bone metastases samples appears to reflect the PIK3CA mutation status in the primary tumour. Breast cancer patients with bone metastases may be candidates for treatment with selective PIK3CA inhibitors.

BRMS1L inhibits bone metastasis of breast cancer cells through epigenetic silence of CXCR4.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13002-e13002
Author(s):  
Yinghuan Cen ◽  
Chang Gong ◽  
Jun Li ◽  
Gehao Liang ◽  
Zihao Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Qrt Pcr ◽  
Metastatic Sites

e13002 Background: We previously demonstrated that BRMS1L (breast cancer metastasis suppressor 1 like) suppresses breast cancer metastasis through HDAC1 recruitment and histone H3K9 deacetylation at the promoter of FZD10, a receptor for Wnt signaling. It is still unclear whether BRMS1L regulates organ-specific metastases, such as bone metastasis, the most prevalent metastatic site of breast cancer. Methods: Examination of the expression of BRMS1L in primary tumors, bone metastatic and other metastatic tissues from breast cancer patients was implemented using qRT-PCR and immunohistochemistry staining. To investigate the mechanism by which BRMS1L drives breast cancer bone metastasis, we tested the mRNA expression by qRT-PCR of a set of potential bone related genes (BRGs) based on PubMed database in MDA-MB-231 cells over expressing BRMS1L and MCF-7 cells knocking-down BRMS1L, and detected the expression of CXCR4 in these established cells by western blot. Transwell assays were performed to assess the migration abilities of breast cancer cells towards osteoblasts. ChIP (Chromatin Immuno-Precipitation) were employed to test the interaction between BRMS1L and CXCR4. Results: At both mRNA and protein levels, the expression of BRMS1L was significantly lower in bone metastatic sites than that in primary cancer tissues and other metastatic sites of breast cancer patients. CXCR4 was screened out in a set of BRGs and negatively correlated with the expression of BRMS1L in breast cancer cell lines. BRMS1L inhibited the migration of breast cancer cells towards osteoblasts through CXCL12/CXCR4 axis. In the presence of TSA treatment, breast cancer cell lines showed an increased expression of CXCR4 in a TSA concentration-dependent manner. In addition, ChIP assays verified that BRMS1L directly bound to the promoter region of CXCR4 and inhibited its transcription through promoter histone deacetylation. Conclusions: BRMS1L mediates the migration abilities of breast cancer cells to bone microenvironment via targeting CXCR4 and contributes to bone metastasis of breast cancer cells. Thus, BRMS1L may be a potential biomarker for predicting bone metastasis in breast cancer.

scholarly journals Cancer-educated mesenchymal stem cells promote the survival of cancer cells at primary and distant metastatic sites via the expansion of bone marrow-derived-PMN-MDSCs

2019 ◽  
Vol 10 (12) ◽  
Author(s):  
Buqing Sai ◽  
Yafei Dai ◽  
Songqing Fan ◽  
Fan Wang ◽  
Lujuan Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Primary Tumour ◽  
Lung Cancer Cells ◽  
Gm Csf ◽  
Metastatic Sites

AbstractBone marrow mesenchymal stem cells (BMSCs) are multipotent stromal cells that can differentiate into a variety of cell types. BMSCs are chemotactically guided towards the cancer cells and contribute to the formation of a cancer microenvironment. The homing of BMSCs was affected by various factors. Disseminated tumour cells (DTCs) in distant organs, especially in the bone marrow, are the source of cancer metastasis and cancer relapse. DTC survival is also determined by the microenvironment. Here we aim to elucidate how cancer-educated BMSCs promote the survival of cancer cells at primary tumour sites and distant sites. We highlight the dynamic change by identifying different gene expression signatures in intratumoral BMSCs and in BMSCs that move back in the bone marrow. Intratumoral BMSCs acquire high mobility and displayed immunosuppressive effects. Intratumoral BMSCs that ultimately home to the bone marrow exhibit a strong immunosuppressive function. Cancer-educated BMSCs promote the survival of lung cancer cells via expansion of MDSCs in bone marrow, primary tumour sites and metastatic sites. These Ly6G+ MDSCs suppress proliferation of T cells. CXCL5, nitric oxide and GM-CSF produced by cancer-educated BMSCs contribute to the formation of malignant microenvironments. Treatment with CXCL5 antibody, the iNOS inhibitor 1400w and GM-CSF antibody reduced MDSC expansion in the bone marrow, primary tumour sites and metastatic sites, and promoted the efficiency of PD-L1 antibody. Our study reveals that cancer-educated BMSCs are the component of the niche for primary lung cancer cells and DTCs, and that they can be the target for immunotherapy.

Detection of breast cancer cells in the bone marrow of early breast cancer patients using quantitative RT PCR for CEA

2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 9638-9638
Author(s):  
F. Janku ◽  
G. Korinkova ◽  
J. Srovnal ◽  
Z. Kleibl ◽  
J. Novotny ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Early Breast Cancer ◽  
Breast Cancer Cells ◽  
Breast Cancer Patients ◽  
Rt Pcr

Changes in the peripheral blood and bone marrow from untreated advanced breast cancer patients that are associated with the establishment of bone metastases

2013 ◽  
Vol 31 (2) ◽  
pp. 213-232 ◽  
Author(s):  
Leandro Marcelo Martinez ◽  
Valeria Beatriz Fernández Vallone ◽  
Vivian Labovsky ◽  
Hosoon Choi ◽  
Erica Leonor Hofer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Advanced Breast Cancer ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Advanced Breast ◽  
Breast Cancer Patients

scholarly journals Selenium donors inhibits osteoclastogenesis through inhibiting IL-6 and plays a pivotal role in bone metastasis from breast cancer

2020 ◽  
Vol 9 (4) ◽  
pp. 544-551
Author(s):  
Luyan Zhang ◽  
Xifa Wu ◽  
Yong Feng ◽  
Linlin Zheng ◽  
Jinbo Jian
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Bone Metastases ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Cellular Level ◽  
Cancer Prognosis ◽  
Breast Cancer Patients ◽  
Dietary Selenium ◽  
Organic Selenium

Abstract Bone metastases are a frequent complication of breast cancer, and there has been little progress in the treatment of breast cancer patients with bone metastases. The cytotoxicity of selenium donors, including organic selenium and selenium nanoparticles (SeNPs), to cancer cells has been reported previously, but their relationship with bone metastases progression is not fully clear yet. In this study, multicenter clinical exploration was conducted to obtain dietary selenium intakes of breast cancer patients with or without bone metastasis, to study the relationship between selenium and breast cancer prognosis and bone metastasis. We found that dietary selenium intakes were significantly lower in breast cancer patients with bone metastasis, comparing with the non-bone metastasis cases. Selenium lower group of bone metastasis breast cancer patients had worse prognosis, whereas the daily selenium intakes could not predict the prognosis of breast cancer patients without bone metastasis. Subsequently, we study the regulatory role of selenium donors on bone metastasis at the cellular level, by challenging the cells with SeNPs. SeNPs showed potent cytotoxicity in breast cancer cells, no matter whether they were primary or bone-metastatic. SeNPs treated cancer cell inhibited the survival and differentiation of osteoclast progenitor cells. At the molecular level, we demonstrated that IL-6 partially mediated osteoclastogenesis suppression by SeNPs. These results provide a new way for biomarkers or drug development to treat and even prevent bone metastases of breast cancer by using selenium donors.

scholarly journals Leptin, Adiponectin, and Sam68 in Bone Metastasis from Breast Cancer

2020 ◽  
Vol 21 (3) ◽  
pp. 1051 ◽  
Author(s):  
Paola Maroni
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Rna Binding ◽  
Tumour Progression ◽  
Primary Tumour ◽  
Fatal Outcome ◽  
Skeletal Metastases ◽  
Neoplastic Disease

The most serious aspect of neoplastic disease is the spread of cancer cells to secondary sites. Skeletal metastases can escape detection long after treatment of the primary tumour and follow-up. Bone tissue is a breeding ground for many types of cancer cells, especially those derived from the breast, prostate, and lung. Despite advances in diagnosis and therapeutic strategies, bone metastases still have a profound impact on quality of life and survival and are often responsible for the fatal outcome of the disease. Bone and the bone marrow environment contain a wide variety of cells. No longer considered a passive filler, bone marrow adipocytes have emerged as critical contributors to cancer progression. Released by adipocytes, adipokines are soluble factors with hormone-like functions and are currently believed to affect tumour development. Src-associated in mitosis of 68 kDa (Sam68), originally discovered as a protein physically associated with and phosphorylated by c-Src during mitosis, is now recognised as an important RNA-binding protein linked to tumour onset and progression of disease. Sam68 also regulates splicing events and recent evidence reports that dysregulation of these events is a key step in neoplastic transformation and tumour progression. The present review reports recent findings on adipokines and Sam68 and their role in breast cancer progression and metastasis.

Gene expression differences between disseminated tumor cells and tumor cells from overt bone metastases in patients with metastatic breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1040-1040
Author(s):  
R. J. Broom ◽  
E. Amir ◽  
T. Cawthorn ◽  
O. Freedman ◽  
D. Gianfelice ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Bone Marrow ◽  
Bone Metastases ◽  
Tumor Cells ◽  
Disseminated Tumor Cells ◽  
Genetic Alterations ◽  
Differentially Expressed ◽  
Primary Tumors ◽  
Ct Guided

1040 Background: Despite extensive work evaluating molecular differences between primary tumors, circulating tumor cells, disseminated tumor cells (DTCs) and established metastases, it is not apparent which genetic alterations are required to form viable, independent bone metastases (BM). A major limitation in exploring the genetic differences between DTCs and established BM is the paucity of fresh BM tissue available. Methods: Ten breast cancer patients with BM underwent a CT-guided BM biopsy and a bone marrow aspiration (for DTCs). Tumor cells were enriched by immunomagnetic separation and RNA was extracted from each sample. Gene expression profiling was conducted using Illumina Human Ref-8 bead arrays. Microarray data was analyzed using BeadStudio software to identify differentially expressed genes. Ingenuity Pathway Analysis software was used to identify genes integral to specific pathways involved in tumor dissemination. Results: The yield of analyzable malignant cells from BM and bone marrow aspirates was 60% and 80%, respectively. A signature of 133 genes was identified that was differentially expressed between the two sample types. Paired analysis of samples from the same patients identified a subset of 161 genes, of which 52 overlapped with the initial unmatched signature. Several genes relevant to breast cancer metastasis to bone (i.e., osteopontin, CTGF, parathyroid hormone receptor, EGFR) were significantly over-expressed in the BM compared to the DTCs. Conclusions: Results suggest that there are specific subsets of genes, which are required for DTCs in the bone marrow to form overt BM. A number of genes identified are already known to participate in osteolytic BM formation. This signature may allow identification of patients at increased risk for developing BM. No significant financial relationships to disclose.

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