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Published in: Tumor Biology 4/2014

01-04-2014 | Research Article

Walker 256/B malignant breast cancer cells improve femur angioarchitecture and disrupt hematological parameters in a rat model of tumor osteolysis

Authors: Riadh Badraoui, Mariem Boubakri, Maissa Bedbabiss, Hmed Ben-Nasr, Tarek Rebai

Published in: Tumor Biology | Issue 4/2014

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Abstract

This study was designed to assess femur angioarchitecture and hematological effects of Walker 256/B cells in a rat model of tumor osteolysis. Tumor osteolysis was induced by in situ inoculation of Walker 256/B malignant cells. Six other rats were sham operated and served as control. Twenty days later, rats were euthanized, and femurs were collected than radiographed. Angioarchitecture [mean lumen diameter (MLD), wall thickness (WTh), Vessel number, volume, and separation (VNb, VV, and VSp respectively)] was studied by histomorphometry at 2 different positions (P1: diaphysis, and P2: metaphysis) of the operated femora. Some hematological parameters were also assessed. Walker 256/B induced marked tumor osteolysis, with cortical perforation and trabecular destruction, associated increase in bone vascularization (increases of VNb and VV and decrease of VSp). Angioarchitecture of W256/B rats was disorganized and showed large MLD and lower WTh. These effects were more prominent in P2. When compared to Sham group, significantly decreases at levels of red blood cell (RBC), hemoglobin (Hb), hematocrit (Ht), and white blood cell (WBC) were observed in W256/B rats. These results suggest that Walker 256/B cells induced tumor osteolysis, improve hypervasculature especially near the tumoral foci (P2) associated hematological disruption. Besides, tumor vessels showed abnormal (enlarged and thinner) and disorganized morphology.
Literature
1.
go back to reference Kerba M, Wu JS, Duan Q, Hagen NA, Bennett MI. Neuropathic pain features in patients with bone metastases referred for palliative radiotherapy. J Clin Oncol. 2010;28:4892–7.PubMedCrossRef Kerba M, Wu JS, Duan Q, Hagen NA, Bennett MI. Neuropathic pain features in patients with bone metastases referred for palliative radiotherapy. J Clin Oncol. 2010;28:4892–7.PubMedCrossRef
2.
go back to reference Fong JE, Le Nihouannen D, Komarova SV. Tumor-supportive and osteoclastogenic changes induced by breast cancer-derived factors are reversed by inhibition of g-secretase. J Biol Chem. 2010;285:31427–34.PubMedCentralPubMedCrossRef Fong JE, Le Nihouannen D, Komarova SV. Tumor-supportive and osteoclastogenic changes induced by breast cancer-derived factors are reversed by inhibition of g-secretase. J Biol Chem. 2010;285:31427–34.PubMedCentralPubMedCrossRef
4.
go back to reference Santini D, Perrone G, Roato I, Godio L, Pantano F, Grasso D, et al. Expression pattern of receptor activator of NFκB (RANK) in a series of primary solid tumors and related metastases. J Cell Physiol. 2011;226:780–4. Santini D, Perrone G, Roato I, Godio L, Pantano F, Grasso D, et al. Expression pattern of receptor activator of NFκB (RANK) in a series of primary solid tumors and related metastases. J Cell Physiol. 2011;226:780–4.
5.
go back to reference Tiedemann K, Hussein O, Sadvakassova G, Guo Y, Siegel PM, Komarova SV. Breast cancer-derived factors stimulate osteoclastogenesis through the Ca2+/protein kinase C and transforming growth factor-beta/MAPK signaling pathways. J Biol Chem. 2009;284:33662–70.PubMedCentralPubMedCrossRef Tiedemann K, Hussein O, Sadvakassova G, Guo Y, Siegel PM, Komarova SV. Breast cancer-derived factors stimulate osteoclastogenesis through the Ca2+/protein kinase C and transforming growth factor-beta/MAPK signaling pathways. J Biol Chem. 2009;284:33662–70.PubMedCentralPubMedCrossRef
6.
go back to reference Bhat TA, Singh RP. Tumor angiogenesis—a potential target in cancer chemoprevention. Food Chem Toxicol. 2008;46:1334–45.PubMedCrossRef Bhat TA, Singh RP. Tumor angiogenesis—a potential target in cancer chemoprevention. Food Chem Toxicol. 2008;46:1334–45.PubMedCrossRef
8.
go back to reference Sterling JA, Edwards JR, Martin TJ, Mundy GR. Advances in the biology of bone metastasis: how the skeleton affects tumor behavior. Bone 2011;48(1):6–15 Sterling JA, Edwards JR, Martin TJ, Mundy GR. Advances in the biology of bone metastasis: how the skeleton affects tumor behavior. Bone 2011;48(1):6–15
9.
go back to reference Desgrosellier JS, Cheresh DA. Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer. 2010;10:9–22.PubMedCrossRef Desgrosellier JS, Cheresh DA. Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer. 2010;10:9–22.PubMedCrossRef
10.
go back to reference Drevs J. VEGF and angiogenesis: implications for breast cancer therapy. Eur J Cancer. 2008;6:7–13.CrossRef Drevs J. VEGF and angiogenesis: implications for breast cancer therapy. Eur J Cancer. 2008;6:7–13.CrossRef
11.
go back to reference Cackowski FC, Anderson JL, Patrene KD, Choksi RJ, Shapiro SD, Windle JJ, et al. Osteoclasts are important for bone angiogenesis. Blood. 2010;115:140–9.PubMedCrossRef Cackowski FC, Anderson JL, Patrene KD, Choksi RJ, Shapiro SD, Windle JJ, et al. Osteoclasts are important for bone angiogenesis. Blood. 2010;115:140–9.PubMedCrossRef
12.
go back to reference Collet G, Skrzypek K, Grillon C, Matejuk A, Hafni-Rahbi BE, Lamerant-Fayel N, et al. Hypoxia control to normalize pathologic angiogenesis: potential role for endothelial precursor cells and miRNAs regulation. Vasc Pharmacol. 2012;56:252–61.CrossRef Collet G, Skrzypek K, Grillon C, Matejuk A, Hafni-Rahbi BE, Lamerant-Fayel N, et al. Hypoxia control to normalize pathologic angiogenesis: potential role for endothelial precursor cells and miRNAs regulation. Vasc Pharmacol. 2012;56:252–61.CrossRef
13.
go back to reference Hiraga T, Kizaka-Kondoh S, Hirota K, Hiraoka M, Yoneda T. Hypoxia and hypoxia-inducible factor-1 expression enhance osteolytic bone metastases of breast cancer. Cancer Res. 2007;67:4157–63.PubMedCrossRef Hiraga T, Kizaka-Kondoh S, Hirota K, Hiraoka M, Yoneda T. Hypoxia and hypoxia-inducible factor-1 expression enhance osteolytic bone metastases of breast cancer. Cancer Res. 2007;67:4157–63.PubMedCrossRef
14.
go back to reference Lynch CC. Matrix metalloproteinases as master regulators of the vicious cycle of bone metastasis. Bone. 2011;48:44–53.PubMedCrossRef Lynch CC. Matrix metalloproteinases as master regulators of the vicious cycle of bone metastasis. Bone. 2011;48:44–53.PubMedCrossRef
15.
go back to reference Shojaei F. Anti-angiogenesis therapy in cancer: Current challenges and future perspectives. Cancer Lett. 2012;320:130–7.PubMedCrossRef Shojaei F. Anti-angiogenesis therapy in cancer: Current challenges and future perspectives. Cancer Lett. 2012;320:130–7.PubMedCrossRef
16.
go back to reference Heymann D. Anti-RANKL therapy for bone tumours: basic, pre-clinical and clinical evidences. J Bone Oncol. 2012;1:2–11.CrossRef Heymann D. Anti-RANKL therapy for bone tumours: basic, pre-clinical and clinical evidences. J Bone Oncol. 2012;1:2–11.CrossRef
17.
go back to reference Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science. 2005;307:58–62.PubMedCrossRef Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science. 2005;307:58–62.PubMedCrossRef
18.
go back to reference Mastro AM, Gay CV, Welch DR. The skeleton as a unique environment for breast cancer cells. Clin Exp Metastasis. 2003;20:275–84.PubMedCrossRef Mastro AM, Gay CV, Welch DR. The skeleton as a unique environment for breast cancer cells. Clin Exp Metastasis. 2003;20:275–84.PubMedCrossRef
19.
go back to reference Bussard KM, Gay CV, Mastro AM. The bone microenvironment in metastasis; what is special about bone? Cancer Metastasis Rev. 2008;27:41–55.PubMedCrossRef Bussard KM, Gay CV, Mastro AM. The bone microenvironment in metastasis; what is special about bone? Cancer Metastasis Rev. 2008;27:41–55.PubMedCrossRef
20.
21.
go back to reference Houssami N, Costelloe CM. Imaging bone metastases in breast cancer: evidence on comparative test accuracy. Ann Oncol. 2012;23:834–43.PubMedCrossRef Houssami N, Costelloe CM. Imaging bone metastases in breast cancer: evidence on comparative test accuracy. Ann Oncol. 2012;23:834–43.PubMedCrossRef
22.
go back to reference Badraoui R, Rebai T. Effect of malignant ascites on antioxidative potency of two tumoral cells-induced bone metastases: Walker 256/B and MatLyLu. Exp Toxicol Pathol. 2012;64:65–8.PubMedCrossRef Badraoui R, Rebai T. Effect of malignant ascites on antioxidative potency of two tumoral cells-induced bone metastases: Walker 256/B and MatLyLu. Exp Toxicol Pathol. 2012;64:65–8.PubMedCrossRef
23.
go back to reference Badraoui R, Blouin S, Moreau MF, Gallois Y, Rebai T, Sahnoun Z, et al. Effect of alpha tocopherol acetate in Walker 256/B cells-induced oxidative damage in a rat model of breast cancer skeletal metastases. Chem Biol Interact. 2009;182:98–105.PubMedCrossRef Badraoui R, Blouin S, Moreau MF, Gallois Y, Rebai T, Sahnoun Z, et al. Effect of alpha tocopherol acetate in Walker 256/B cells-induced oxidative damage in a rat model of breast cancer skeletal metastases. Chem Biol Interact. 2009;182:98–105.PubMedCrossRef
24.
go back to reference Mao-Ying QL, Zhao J, Dong ZQ, Wang J, Yu J, Yan MF, et al. A rat model of bone cancer pain induced by intra-tibia inoculation of Walker 256/B mammary gland carcinoma cells. Biochem Biophys Res Commun. 2006;345:1292–8.PubMedCrossRef Mao-Ying QL, Zhao J, Dong ZQ, Wang J, Yu J, Yan MF, et al. A rat model of bone cancer pain induced by intra-tibia inoculation of Walker 256/B mammary gland carcinoma cells. Biochem Biophys Res Commun. 2006;345:1292–8.PubMedCrossRef
25.
go back to reference Blouin S, Moreau MF, Baslé MF, Chappard D. Relations between radiograph texture analysis and microcomputed tomography in two rat model of bone metastases. Cells Tissues Organs. 2006;182:182–92.PubMedCrossRef Blouin S, Moreau MF, Baslé MF, Chappard D. Relations between radiograph texture analysis and microcomputed tomography in two rat model of bone metastases. Cells Tissues Organs. 2006;182:182–92.PubMedCrossRef
26.
go back to reference Chappard D, Bouvard B, Baslé MF, Legrand E, Audran M. Bone metastasis: Histological changes and pathophysiological mechanisms in osteolytic or osteosclerotic localizations. A review. Morphologie. 2011;95:65–75.PubMedCrossRef Chappard D, Bouvard B, Baslé MF, Legrand E, Audran M. Bone metastasis: Histological changes and pathophysiological mechanisms in osteolytic or osteosclerotic localizations. A review. Morphologie. 2011;95:65–75.PubMedCrossRef
27.
go back to reference Chappard D, Libouban H, Legrand E, Ifrah N, Masson C, Baslé MF, et al. Computed microtomography of bone specimens for rapid analysis of bone changes associated with malignancy. Anat Rec. 2010;293:1125–33.CrossRef Chappard D, Libouban H, Legrand E, Ifrah N, Masson C, Baslé MF, et al. Computed microtomography of bone specimens for rapid analysis of bone changes associated with malignancy. Anat Rec. 2010;293:1125–33.CrossRef
28.
29.
go back to reference Portal-Núñez S, Lozano D, Esbrit P. Role of angiogenesis on bone formation. Histol Histopathol. 2012;27:559–66.PubMed Portal-Núñez S, Lozano D, Esbrit P. Role of angiogenesis on bone formation. Histol Histopathol. 2012;27:559–66.PubMed
30.
go back to reference Nyangoga H, Mercier P, Libouban H, Basle MF, Chappard D. Three-dimensional characterization of the vascular bed in bone metastasis of the rat by microcomputed tomography (MicroCT). PLoS ONE. 2011;6:e17336.PubMedCentralPubMedCrossRef Nyangoga H, Mercier P, Libouban H, Basle MF, Chappard D. Three-dimensional characterization of the vascular bed in bone metastasis of the rat by microcomputed tomography (MicroCT). PLoS ONE. 2011;6:e17336.PubMedCentralPubMedCrossRef
31.
go back to reference Etoh T, Inoue H, Tanaka S, Barnard GF, Kitano S, Mori M. Angiopoietin-2 is related to tumor angiogenesis in gastric carcinoma: possible in vivo regulation via induction of proteases. Cancer Res. 2001;61:2145–53.PubMed Etoh T, Inoue H, Tanaka S, Barnard GF, Kitano S, Mori M. Angiopoietin-2 is related to tumor angiogenesis in gastric carcinoma: possible in vivo regulation via induction of proteases. Cancer Res. 2001;61:2145–53.PubMed
32.
go back to reference Guise TA, Kozlow WM, Heras-Herig A, Padalecki SS, Yin JJ, Chirgwin JM. Molecular mechanisms of breast cancer metastases to bone. Clin Breast Cancer. 2005;5:S46–53.PubMedCrossRef Guise TA, Kozlow WM, Heras-Herig A, Padalecki SS, Yin JJ, Chirgwin JM. Molecular mechanisms of breast cancer metastases to bone. Clin Breast Cancer. 2005;5:S46–53.PubMedCrossRef
33.
go back to reference Ellis SL, Grassinger J, Jones A, Camenisch T, Haylock D, Bertoncello I, et al. The relationship between bone, hemopoietic stem cells, and vasculature. Blood. 2011;118:1516–24.PubMedCrossRef Ellis SL, Grassinger J, Jones A, Camenisch T, Haylock D, Bertoncello I, et al. The relationship between bone, hemopoietic stem cells, and vasculature. Blood. 2011;118:1516–24.PubMedCrossRef
34.
go back to reference Jiang Y, Bonig H, Ulyagova T, Chang K, Papayannopoulou T. On the adaptation of endosteal stem cell niche function in response to stress. Blood. 2009;114:3773–82.PubMedCentralPubMedCrossRef Jiang Y, Bonig H, Ulyagova T, Chang K, Papayannopoulou T. On the adaptation of endosteal stem cell niche function in response to stress. Blood. 2009;114:3773–82.PubMedCentralPubMedCrossRef
35.
go back to reference Roux S, Mariette X. Hematological malignancies and the bone (myeloma excluded). Joint Bone Spine. 2000;67:264–71.PubMed Roux S, Mariette X. Hematological malignancies and the bone (myeloma excluded). Joint Bone Spine. 2000;67:264–71.PubMed
36.
go back to reference Iriuchishima H, Takubo K, Miyakawa Y, Nakamura-Ishizu A, Miyauchi Y, Fujita N, et al. Neovascular niche for human myeloma cells in immunodeficient mouse bone. PLoS ONE. 2012;7:e30557.PubMedCentralPubMedCrossRef Iriuchishima H, Takubo K, Miyakawa Y, Nakamura-Ishizu A, Miyauchi Y, Fujita N, et al. Neovascular niche for human myeloma cells in immunodeficient mouse bone. PLoS ONE. 2012;7:e30557.PubMedCentralPubMedCrossRef
37.
go back to reference Caolo V, Molin DGM, Post MJ. Notch Regulation of Hematopoiesis, Endothelial Precursor Cells, and Blood Vessel Formation: Orchestrating the Vasculature. Stem Cells Int. 2012 doi:10.1155/2012/805602. Caolo V, Molin DGM, Post MJ. Notch Regulation of Hematopoiesis, Endothelial Precursor Cells, and Blood Vessel Formation: Orchestrating the Vasculature. Stem Cells Int. 2012 doi:10.​1155/​2012/​805602.
38.
go back to reference Kwon JH, Shin JH, Kim JH, Gwon DI, Yoon HK, Ko GY, et al. Preoperative transcatheter arterial embolization of hypervascular metastatic tumors of long bones. Acta Radiol. 2010;51:396–401.PubMedCrossRef Kwon JH, Shin JH, Kim JH, Gwon DI, Yoon HK, Ko GY, et al. Preoperative transcatheter arterial embolization of hypervascular metastatic tumors of long bones. Acta Radiol. 2010;51:396–401.PubMedCrossRef
39.
go back to reference Palli D, Berrino F, Vineis P, Tumino R, Panico S, Masala G, et al. A molecular epidemiology project on diet and cancer: the EPIC-Italy prospective study. Design and baseline characteristics of participants. Tumori. 2003;89:586–93.PubMed Palli D, Berrino F, Vineis P, Tumino R, Panico S, Masala G, et al. A molecular epidemiology project on diet and cancer: the EPIC-Italy prospective study. Design and baseline characteristics of participants. Tumori. 2003;89:586–93.PubMed
40.
go back to reference De Vizcaya-Ruiz A, Rivero-Muller A, Ruiz-Ramirez L, Howarth JA, Dobrota M. Hematotoxicity response in rats by the novel copper-based anticancer agent: casiopeina II. Toxicology. 2003;194:103–13.PubMedCrossRef De Vizcaya-Ruiz A, Rivero-Muller A, Ruiz-Ramirez L, Howarth JA, Dobrota M. Hematotoxicity response in rats by the novel copper-based anticancer agent: casiopeina II. Toxicology. 2003;194:103–13.PubMedCrossRef
Metadata
Title
Walker 256/B malignant breast cancer cells improve femur angioarchitecture and disrupt hematological parameters in a rat model of tumor osteolysis
Authors
Riadh Badraoui
Mariem Boubakri
Maissa Bedbabiss
Hmed Ben-Nasr
Tarek Rebai
Publication date
01-04-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 4/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1485-5

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