P57. Manipulating the bone mineral affinity of bisphosphonates to directly target cancer cells in the bone marrow

2008 ◽  
Vol 34 ◽  
pp. 42
Author(s):  
Florence Daubiné ◽  
Pierrick Fournier ◽  
Hal Ebetino ◽  
Philippe Clezardin
Keyword(s):  
Bone Marrow ◽  
Cancer Cells ◽  
Bone Mineral ◽  
Target Cancer

scholarly journals Inhibition of glypican-1 expression induces an activated fibroblast phenotype in a human bone marrow-derived stromal cell-line

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sukhneeraj P. Kaur ◽  
Arti Verma ◽  
Hee. K. Lee ◽  
Lillie M. Barnett ◽  
Payaningal R. Somanath ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Stromal Cell ◽  
Prostate Cancer Cell ◽  
Bone Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Prostate Cancer Cells

AbstractCancer-associated fibroblasts (CAFs) are the most abundant stromal cell type in the tumor microenvironment. CAFs orchestrate tumor-stromal interactions, and contribute to cancer cell growth, metastasis, extracellular matrix (ECM) remodeling, angiogenesis, immunomodulation, and chemoresistance. However, CAFs have not been successfully targeted for the treatment of cancer. The current study elucidates the significance of glypican-1 (GPC-1), a heparan sulfate proteoglycan, in regulating the activation of human bone marrow-derived stromal cells (BSCs) of fibroblast lineage (HS-5). GPC-1 inhibition changed HS-5 cellular and nuclear morphology, and increased cell migration and contractility. GPC-1 inhibition also increased pro-inflammatory signaling and CAF marker expression. GPC-1 induced an activated fibroblast phenotype when HS-5 cells were exposed to prostate cancer cell conditioned media (CCM). Further, treatment of human bone-derived prostate cancer cells (PC-3) with CCM from HS-5 cells exhibiting GPC-1 loss increased prostate cancer cell aggressiveness. Finally, GPC-1 was expressed in mouse tibia bone cells and present during bone loss induced by mouse prostate cancer cells in a murine prostate cancer bone model. These data demonstrate that GPC-1 partially regulates the intrinsic and extrinsic phenotype of human BSCs and transformation into activated fibroblasts, identify novel functions of GPC-1, and suggest that GPC-1 expression in BSCs exerts inhibitory paracrine effects on the prostate cancer cells. This supports the hypothesis that GPC-1 may be a novel pharmacological target for developing anti-CAF therapeutics to control cancer.

scholarly journals Targeting E-selectin to Tackle Cancer Using Uproleselan

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 335
Author(s):  
Barbara Muz ◽  
Anas Abdelghafer ◽  
Matea Markovic ◽  
Jessica Yavner ◽  
Anupama Melam ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Metastatic Tumor ◽  
Therapy Resistance ◽  
Surface Proteins ◽  
Cell Trafficking ◽  
Primary Role ◽  
Novel Therapy ◽  
Tumor Dissemination

E-selectin is a vascular adhesion molecule expressed mainly on endothelium, and its primary role is to facilitate leukocyte cell trafficking by recognizing ligand surface proteins. E-selectin gained a new role since it was demonstrated to be involved in cancer cell trafficking, stem-like properties and therapy resistance. Therefore, being expressed in the tumor microenvironment, E-selectin can potentially be used to eradicate cancer. Uproleselan (also known as GMI-1271), a specific E-selectin antagonist, has been tested on leukemia, myeloma, pancreatic, colon and breast cancer cells, most of which involve the bone marrow as a primary or as a metastatic tumor site. This novel therapy disrupts the tumor microenvironment by affecting the two main steps of metastasis—extravasation and adhesion—thus blocking E-selectin reduces tumor dissemination. Additionally, uproleselan mobilized cancer cells from the protective vascular niche into the circulation, making them more susceptible to chemotherapy. Several preclinical and clinical studies summarized herein demonstrate that uproleselan has favorable safety and pharmacokinetics and is a tumor microenvironment-disrupting agent that improves the efficacy of chemotherapy, reduces side effects such as neutropenia, intestinal mucositis and infections, and extends overall survival. This review highlights the critical contribution of E-selectin and its specific antagonist, uproleselan, in the regulation of cancer growth, dissemination, and drug resistance in the context of the bone marrow microenvironment.

scholarly journals Intra-Bone Marrow Administration of Mesenchymal Stem/Stromal Cells Is a Promising Approach for Treating Osteoporosis

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Hideki Agata ◽  
Yoshinori Sumita ◽  
Tatsuro Hidaka ◽  
Mayumi Iwatake ◽  
Hideaki Kagami ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Mineral Content ◽  
Bone Mineral ◽  
Intravenous Administration ◽  
Stromal Cells ◽  
Mineral Content ◽  
Bone Diseases ◽  
Research Progress ◽  
Bone Thickness ◽  
Mineral Density

Mesenchymal stem/stromal cells (MSCs) are known to be useful for treating local bone diseases. However, it is not known if MSCs are effective for treating systemic bone diseases, as the risk for mortality following intravenous MSC administration has hindered research progress. In this study, we compared the safety and efficacy of intra-bone marrow and intravenous administration of MSCs for the treatment of ovariectomy- (OVX-) induced osteoporosis. Cells capable of forming bone were isolated from the murine compact bones and expanded in culture. Relatively pure MSCs possessing increased potential for cell proliferation, osteogenic differentiation, and inhibition of osteoclastogenesis were obtained by magnetic-activated cell sorting with the anti-Sca-1 antibody. Sca-1-sorted MSCs were administered to OVX mice, which were sacrificed 1 month later. We observed that 22% of the mice died after intravenous administration, whereas none of the mice died after intra-bone marrow administration. With respect to efficacy, intravenous administration improved bone mineral density (BMD) by increasing bone mineral content without affecting bone thickness, whereas intra-bone marrow administration improved BMD by increasing both bone mineral content and bone thickness. These results indicate that intra-bone marrow administration of pure MSCs is a safer and more effective approach for treating osteoporosis.

Bone Marrow/Bone Pre-Metastatic Niche For Breast Cancer Cells Colonization: The Role Of Mesenchymal Stromal Cells

2021 ◽  
pp. 103416
Author(s):  
M.C. Sanmartin ◽  
F.R. Borzone ◽  
M.B. Giorello ◽  
N. Pacienza ◽  
G. Yannarelli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cancer Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Breast Cancer Cells ◽  
Metastatic Niche

Hematopoietic bone marrow hyperplasia: correlation of spinal MR findings, hematologic parameters, and bone mineral density in endurance athletes.

Radiology ◽  
1996 ◽  
Vol 198 (2) ◽  
pp. 503-508 ◽  
Author(s):  
K S Caldemeyer ◽  
R R Smith ◽  
A Harris ◽  
T Williams ◽  
Y Huang ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Marrow ◽  
Bone Mineral ◽  
Endurance Athletes ◽  
Mineral Density ◽  
Hematopoietic Bone Marrow

Bone marrow-derived mesenchymal stem cells increase drug resistance in CD133-expressing gastric cancer cells by regulating the PI3K/AKT pathway

Tumor Biology ◽  
2016 ◽  
Vol 37 (11) ◽  
pp. 14637-14651 ◽  
Author(s):  
Nuo Ji ◽  
Ji-Wei Yu ◽  
Xiao-Chun Ni ◽  
Ju-Gang Wu ◽  
Shou-Lian Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Bone Marrow ◽  
Drug Resistance ◽  
Mesenchymal Stem Cells ◽  
Cancer Cells ◽  
Akt Pathway ◽  
Gastric Cancer Cells ◽  
Increase Drug Resistance
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