scholarly journals Oriented collagen fibers direct tumor cell intravasation

2016 ◽  
Vol 113 (40) ◽  
pp. 11208-11213 ◽  
Author(s):  
Weijing Han ◽  
Shaohua Chen ◽  
Wei Yuan ◽  
Qihui Fan ◽  
Jianxiang Tian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Fiber Orientation ◽  
Breast Cancer Cells ◽  
Protein Concentration ◽  
Collagen Fiber ◽  
Fiber Alignment ◽  
Local Fiber

In this work, we constructed a Collagen I–Matrigel composite extracellular matrix (ECM). The composite ECM was used to determine the influence of the local collagen fiber orientation on the collective intravasation ability of tumor cells. We found that the local fiber alignment enhanced cell–ECM interactions. Specifically, metastatic MDA-MB-231 breast cancer cells followed the local fiber alignment direction during the intravasation into rigid Matrigel (∼10 mg/mL protein concentration).

scholarly journals A Nuclear-Directed Ribonuclease Variant Targets Cancer Stem Cells and Inhibits Migration and Invasion of Breast Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4350
Author(s):  
Jessica Castro ◽  
Giusy Tornillo ◽  
Gerardo Ceada ◽  
Beatriz Ramos-Neble ◽  
Marlon Bravo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cell Lines ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Tumor Cell Lines

Despite the significant advances in cancer research made in recent years, this disease remains one of the leading causes of death worldwide. In part, this is due to the fact that after therapy, a subpopulation of self-renewing tumor cells can survive and promote cancer relapse, resistance to therapies and metastasis. Targeting these cancer stem cells (CSCs) is therefore essential to improve the clinical outcome of cancer patients. In this sense, multi-targeted drugs may be promising agents targeting CSC-associated multifocal effects. We have previously constructed different human pancreatic ribonuclease (RNase) variants that are cytotoxic for tumor cells due to a non-classical nuclear localization signal introduced in their sequence. These cytotoxic RNases affect the expression of multiple genes involved in deregulated metabolic and signaling pathways in cancer cells and are highly cytotoxic for multidrug-resistant tumor cell lines. Here, we show that these cytotoxic nuclear-directed RNases are highly selective for tumor cell lines grown in 3D, inhibit CSCs’ development and diminish the self-renewal capacity of the CSCs population. Moreover, these human RNase variants reduce the migration and invasiveness of highly invasive breast cancer cells and downregulate N-cadherin expression.

Test measuring signaling activity in live patient tumor cells to identify PI3KCA WT patients who may benefit from PI3K inhibitors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13000-e13000
Author(s):  
Lance G. Laing ◽  
Salmaan Khan ◽  
Ian A. MacNeil ◽  
Catherine Kuzmicki ◽  
Benjamin E. Rich ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Breast Cancer Cells ◽  
Pi3k Signaling ◽  
Breast Cancer Patients ◽  
Breast Tumor Cell ◽  
Pi3k Inhibitors ◽  
Live Patient

e13000 Background: Biological factors other than PIK3CA status, such as aberrant GPCR-linked signaling, may be important to measure when identifying patients eligible for PI3K inhibitors. A new assay, the CELx PI3K test, using an impedance biosensor was developed to measure ex vivo live tumor cell response to specific S1P agonists and PI3K antagonists to diagnose breast tumors with PI3K-involved hyperactive signaling. This study set out to: 1) compare CELx PI3K test results and xenograft results using cell lines with PIK3CA mutations; and 2) assess whether PI3K-involved hyperactive S1P signaling is found in PIK3CA WT breast cancer patient tumors. Methods: A panel of 17 fresh HER2-/PIK3CA WT tumor cells from breast cancer patients and three PIK3CA mutated breast tumor cell lines were obtained. Live cell response to an S1P agonist, PI3K-α antagonist (alpelisib), PI3K-γ antagonist (IPI-549), and a pan-PI3K inhibitor (taselisib) were measured using an xCELLigence RTCA impedance biosensor. From these responses, PI3K-involved signaling was quantified and characterized as normal or abnormal using a previously determined cutpoint. For the xenograft study, 16 NSG mice were injected with HCC1954 PIK3CA mutated breast cancer cells and randomly assigned to either the control or taselisib group (10 mg/kg). Results: Four of the 17 PIK3CA WT tumor cells had abnormal levels of combined PI3K-α and PI3K-γ signaling. Only one of the three PIK3CA mutated breast tumor cell lines (BT20) had abnormal levels of PI3K-α and pan-PI3K involved signaling. The HCC1954 cell line had normal PI3K-α and abnormal pan-PI3K signaling. CAL-51 reported normal PI3K-α and pan-PI3K signaling. The normal levels of PI3K-α signaling found in the HCC1954 and CAL-51 cell lines correlated with previously reported xenograft studies that found alpelisib had no anti-tumor effect. The xenograft study reported here using HCC1954 cells found taselisib induces a significant anti-tumor effect (T/C ratio = 0.21; p = 0.009; t-test). Conclusions: A sub-set of PIK3CA WT patient breast cancer tumors had abnormal PI3K-involved signaling comparable to levels found in PI3KCA mutated cell lines. Abnormal pan-PI3K signaling and normal PI3K-α signaling in the HCC1954 cell line correlated with xenograft results. This study thus suggests that measurement of PI3K-involvement in hyperactive S1P signaling in live patient breast cancer cells may provide a means to identify breast cancer patients who may or may not benefit from treatment with PI3K inhibitors.

Interactions of breast cancer cells with the microenvironment of the human bone marrow

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22097-e22097
Author(s):  
T. Kaiser ◽  
G. Klein ◽  
E. Solomayer ◽  
D. Wallwiener ◽  
T. Fehm
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cell Migration ◽  
Cell Adhesion ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Stromal Cells ◽  
Breast Cancer Cells ◽  
Migration Assays

e22097 Background: Bone is one of the most favored sites for metastasis of breast cancer cells (BrCa) resulting in the formation of osteolytic and/or osteoblastic lesions. There is increasing evidence that the bone marrow (BM) microenvironment plays a pivotal role in modulating tumor cell homing to the bone, metastasis and progression. However, the molecular crosstalk between BrCa cells and the cellular and extracellular components of the bone marrow leading to osteotropism still remains a poorly characterized step in the metastatic process. Methods: Cell adhesion and migration assays using the invasive MDA-MB-231 and the noninvasive MCF7 BrCa cell lines were performed to investigate the impact of BM components on cellular functions of tumor cells. Results: Cell-matrix adhesion assays showed a strong and concentration-dependent attachment of BrCa cells to several extracellular matrix components present in the human bone marrow such as fibronectin, different laminin isoforms, collagens type I and IV or tenascin-C. Moreover, the BrCa cells attached avidly to the BM-derived primary osteoblasts, whereas the binding to stromal cells was significantly weaker. Notably, cell-cell adhesion experiments with primary osteoclasts revealed an anti-adhesive effect on tumor cell binding leading to no attachment activity of BrCa cells with the cell surface of primary osteoclasts. The influence of cellular components of the BM on tumor cell migration was analyzed by cell migration assays using conditioned media of osteoblasts, osteoclasts and stromal cells or a modified Transwell chamber technique. The migration assays with invasive MDA-MB-231 cells clearly showed that osteoblasts, but not osteoclasts or stromal cells released factors which led to a faster wound closure, suggesting an enhanced migratory ability of the metastatic tumor cells, whereas the migration of nonmetastatic MCF7 cells was unaffected. Conclusions: These data indicate that the crosstalk with osteoblasts affects both the adhesive and the migratory ability of BrCa cells favoring the bone colonization process. Furthermore, the presented experimental conditions may provide useful tools to study effects of antiresorptive drugs like bisphosphonates to improve therapeutic strategies for treatment metastatic bone disease. No significant financial relationships to disclose.

scholarly journals ANGPTL2 increases bone metastasis of breast cancer cells through enhancing CXCR4 signaling

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Tetsuro Masuda ◽  
Motoyoshi Endo ◽  
Yutaka Yamamoto ◽  
Haruki Odagiri ◽  
Tsuyoshi Kadomatsu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Breast Tumor ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Cxcr4 Expression ◽  
Breast Cancer Patients

Abstract Bone metastasis of breast cancer cells is a major concern, as it causes increased morbidity and mortality in patients. Bone tissue-derived CXCL12 preferentially recruits breast cancer cells expressing CXCR4 to bone metastatic sites. Thus, understanding how CXCR4 expression is regulated in breast cancer cells could suggest approaches to decrease bone metastasis of breast tumor cells. Here, we show that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) increases responsiveness of breast cancer cells to CXCL12 by promoting up-regulation of CXCR4 in those cells. In addition, we used a xenograft mouse model established by intracardiac injection of tumor cells to show that ANGPTL2 knockdown in breast cancer cells attenuates tumor cell responsiveness to CXCL12 by decreasing CXCR4 expression in those cells, thereby decreasing bone metastasis. Finally, we found that ANGPTL2 and CXCR4 expression levels within primary tumor tissues from breast cancer patients are positively correlated. We conclude that tumor cell-derived ANGPTL2 may increase bone metastasis by enhancing breast tumor cell responsiveness to CXCL12 signaling through up-regulation of tumor cell CXCR4 expression. These findings may suggest novel therapeutic approaches to treat metastatic breast cancer.

scholarly journals Increased Cellular Levels of MicroRNA-9 and MicroRNA-221 Correlate with Cancer Stemness and Predict Poor Outcome in Human Breast Cancer

2018 ◽  
Vol 48 (5) ◽  
pp. 2205-2218 ◽  
Author(s):  
Chun-Wen Cheng ◽  
Jyh-Cherng Yu ◽  
Yi-Hsien Hsieh ◽  
Wen-Ling Liao ◽  
Jia-Ching Shieh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Breast Cancer Cells ◽  
Side Population ◽  
Migration And Invasion ◽  
Cell Renewal ◽  
Poor Outcome

Background /Aims: Recent studies of microRNA (miRNA) involvement in tumorigenesis have indicated the critical role of these non-coding small RNAs in malignant transformation, but the prognostic role, if any, of miRNAs in breast cancer remains undetermined. Therefore, we assessed the prognostic significance of microRNA-9 (miR-9) and miR-221 in breast cancer toward the goal of understanding the contribution(s) of these miRNAs to cancer cell stemness. Methods: The level of each of miR-9 and miR-221 in 206 paired laser capture microdissected tumor cells and non-tumor cells was determined by quantitative reverse transcription-PCR (qRT-PCR). The relationship between the miRNA signature and clinicopathological data and prognosis of breast cancer was assessed. Identification of a stem cell-enriched side population was achieved with fluorescence-activated cell sorting and a sphere-forming assay. Wound healing, Boyden chamber assays, and western blotting were used to study the contribution of each miRNA to tumor cell migration and invasion. Results: We found that induction of miR-9 and miR-221 mimics conferred side-population cells to form spheroidal tumor colonies in suspension culture that maintained the mesenchymal stem-cell potential in non-invasive MCF-7 breast cancer cells. In contrast, knockdown of both miR-9 and miR-221 in invasive MDA-MB-231 breast cancer cells dramatically decreased the number of side-population colonies with stem cell-like potency, which reduced the capacity for tumor-cell renewal, invasion, and migration. Clinically, the mean proportion of miR-9- or miR-221-overexpressing cells was significantly greater in tumor cells compared with non-tumor cells (P < 0.05). Increased levels of miR-9 and miR-221 in breast tissue portended a significantly elevated risk of progression to malignancy with respect to larger tumor size, poor differentiation, late-stage evolution, lymph-node metastasis (P < 0.05), and lower overall survival (Ptrend = 0.017; eight-year follow-up). Conclusion: Our findings provide strong evidence that miR-9 and miR-221 can enhance the generation of cancer stem cells to yield an invasive phenotype and that overexpression of these miRNAs predicts a poor outcome for breast cancer patients.

scholarly journals Platelet glycoprotein VI promotes metastasis through interaction with cancer cell-derived Galectin-3

Blood ◽  
2020 ◽  
Author(s):  
Elmina Mammadova-Bach ◽  
Jesus Gil-Pulido ◽  
Edita Sarukhanyan ◽  
Philipp Burkard ◽  
Sergey Shityakov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Breast Cancer Cells ◽  
Platelet Adhesion ◽  
Platelet Glycoprotein ◽  
Glycoprotein Vi ◽  
Galectin 3

Increasing evidence suggests that platelets play a predominant role in colon and breast cancer metastasis but the underlying molecular mechanisms remain elusive. Glycoprotein VI (GPVI) is a platelet-specific receptor for collagen and fibrin that triggers platelet activation through immunoreceptor tyrosine-based activation motif (ITAM)-signaling and thereby regulates diverse functions including platelet adhesion, aggregation and procoagulant activity. GPVI has been proposed as a safe antithrombotic target as its inhibition is protective in models of arterial thrombosis with only minor effects on hemostasis. Here, we demonstrate that genetic deficiency of platelet GPVI in mice decreases experimental and spontaneous metastasis of colon and breast cancer cells. Similar results were obtained with mice lacking the spleen-tyrosine kinase Syk in platelets, an essential component of the ITAM-signaling cascade. In vitro and in vivo analyses show that mouse, as well as human GPVI, supports platelet adhesion to colon and breast cancer cells. Using a CRISPR/Cas9-based gene knock-out approach, we identified Galectin-3 as the major counter-receptor of GPVI on tumor cells. In vivo studies demonstrated that the interplay between platelet GPVI and tumor cell-expressed Galectin-3 utilizes ITAM-signaling components in platelets and favors the extravasation of tumor cells. Finally, we showed that JAQ1 F(ab)2-mediated inhibition of GPVI efficiently impairs platelet-tumor cell interaction and tumor metastasis. Our study reveals a new mechanism by which platelets promote the metastasis of colon and breast cancer cells and suggests that GPVI represents a promising target for antimetastatic therapies.

Recent Advances on Therapeutic Peptides for Breast Cancer Treatment

2020 ◽  
Vol 21 ◽  
Author(s):  
Samad Beheshtirouy ◽  
Farhad Mirzaei ◽  
Shirin Eyvazi ◽  
Vahideh Tarhriz
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Breast Cancer Cells ◽  
Specific Binding ◽  
High Specificity ◽  
The Novel ◽  
Anti Cancer ◽  
Therapeutic Peptides ◽  
Low Toxicity

: Breast cancer is a heterogeneous malignancy which is the second cause of mortality among women in the world. Increasing the resistance to anti-cancer drugs in breast cancer cells persuades researchers to search the novel therapies approaches for the treatment of the malignancy. Among the novel methods, therapeutic peptides which target and disrupt tumor cells have been of great interest. Therapeutic peptides are short amino acids monomer chains with high specificity to bind and modulate a protein interaction of interest. Several advantages of peptides such as specific binding on tumor cells surface, low molecular weight and low toxicity on normal cells make the peptides as an appealing therapeutic agents against solid tumors, particularly breast cancer. Also, National Institutes of Health (NIH) describes therapeutic peptides as suitable candidate for the treatment of drug-resistant breast cancer. In this review, we attempt to review the different therapeutic peptides against breast cancer cells which can be used in treatment and diagnosis of the malignancy. Meanwhile, we presented an overview of peptide vaccines which have been developed for the treatment of breast cancer.

scholarly journals Clusters, Assemblies and Aggregates of Tumor Cells in the Blood of Breast Cancer Patients; Composition, Mode of Action, Detection and Impact on Metastasis and Survival

2021 ◽  
Vol 1 (1) ◽  
pp. 55-68
Author(s):  
Urszula Smietanka ◽  
Małgorzata Szostakowska-Rodzos ◽  
Sylwia Tabor ◽  
Anna Fabisiewicz ◽  
Ewa A. Grzybowska
Keyword(s):  
Breast Cancer ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Diagnostic Tool ◽  
Therapeutic Target ◽  
Mode Of Action ◽  
Breast Cancer Patients ◽  
Single Ctcs ◽  
Methods Of Isolation

Circulating tumor cells (CTCs) are gaining momentum as a diagnostic tool and therapeutic target. CTC clusters are more metastatic, but harder to study and characterize, because they are rare and the methods of isolation are mostly focused on single CTCs. This review highlights the recent advances to our understanding of tumor cell clusters with the emphasis on their composition, origin, biology, methods of detection, and impact on metastasis and survival. New approaches to therapy, based on cluster characteristics are also described.

scholarly journals Single-cell evaluation reveals shifts in the tumor-immune niches that shape and maintain aggressive lesions in the breast

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Vidya C. Sinha ◽  
Amanda L. Rinkenbaugh ◽  
Mingchu Xu ◽  
Xinhui Zhou ◽  
Xiaomei Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Mouse Model ◽  
Transition State ◽  
Tumor Cell ◽  
Single Cell ◽  
Tumor Cells ◽  
Breast Lesions ◽  
Aggressive Tumor ◽  
Insight Into

AbstractThere is an unmet clinical need for stratification of breast lesions as indolent or aggressive to tailor treatment. Here, single-cell transcriptomics and multiparametric imaging applied to a mouse model of breast cancer reveals that the aggressive tumor niche is characterized by an expanded basal-like population, specialization of tumor subpopulations, and mixed-lineage tumor cells potentially serving as a transition state between luminal and basal phenotypes. Despite vast tumor cell-intrinsic differences, aggressive and indolent tumor cells are functionally indistinguishable once isolated from their local niche, suggesting a role for non-tumor collaborators in determining aggressiveness. Aggressive lesions harbor fewer total but more suppressed-like T cells, and elevated tumor-promoting neutrophils and IL-17 signaling, disruption of which increase tumor latency and reduce the number of aggressive lesions. Our study provides insight into tumor-immune features distinguishing indolent from aggressive lesions, identifies heterogeneous populations comprising these lesions, and supports a role for IL-17 signaling in aggressive progression.

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