Expressions of Osteopontin and Related Factors in Breast Cancer Tissues and Its Clinical Significance_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

GU Ming ,  ZHENG Xinyu

Department of Breast Surgery &;
General Surgery， The First Affiliated Hospital of China Medical University， Shenyang 110001， Liaoning Province， China;

Corresponding author：

ZHENG Xinyu, Email: xyzheng126@126.com

Keywords：

Breast cancer; Immunohistochemistry; Osteopontin; Breast tumor kinase; Vascular endothelial growth factor

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Abstract Full text Figures/Tables Video References Cited by

Objective 　To detect the expressions of osteopontin （OPN）， breast tumor kinase （Brk）， and vascular endothelial growth factor （VEGF） in the breast cancer tissue， the adjacent （2cm） normal breast tissue， and the distal
（＞5cm） normal breast tissue， and analyze their clinical significances.
Method 　The immunohistochemical method was used to detect the expressions of OPN， Brk， and VEGF in the breast cancer tissue， the adjacent （2cm） normal breast tissue， and the distal （＞5cm） normal breast tissue from 40 cases of breast cancer. Results　① The expressions of OPN，Brk， and VEGF in the breast cancer tissue were significantly higher than those of the adjacent （2cm） normal breast tissue and the distal （＞5cm） normal breast tissue （P＜0.01）， the expression of Brk in the adjacent （2cm） normal breast tissue was significantly higher than that of the distal （＞5 cm） normal breast tissue （P＜0.05）. ② In the breast cancer tissue， the OPN and Brk protein expressions were not associated with age， tumor diameter， and histological grade （P＞0.05），were associated with lymph node metastasis and TNM stage （P＜0.05）. The VEGF protein expression was not associated with age and tumor diameter （P＞0.05）， but was associated with histological grade， lymph node metastasis， and TNM staging （P＜0.05）. ③ In the breast cancer tissue， OPN， Brk， and VEGF had positive correlation with each other （P＜0.05）， but not in the adjacent （2cm） normal breast tissue and the distal （＞5 cm） normal breast tissue （P＞0.05）.
Conclusions 　The expressions of OPN and Brk from the same signal pathway increase by turns in the distal （＞5 cm） normal breast tissue， adjacent （2cm） normal breast tissue， and breast cancer tissue. OPN induced the adhesion and migration of endothelial cells to accelerate vascular repair through VEGF and Brk has correlation with the progress of tumor invasion and metastasis through participating in tumor vascularization.

Citation： GU Ming,ZHENG Xinyu. Expressions of Osteopontin and Related Factors in Breast Cancer Tissues and Its Clinical Significance. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2013, 20(8): 890-895. doi: Copy

1.	Siegel R， Naishadham D， Jemal A. Cancer statistics， 2012[J]. CA Cancer J Clin， 2012， 62(1)：10-29.
2.	孙杰，罗军，刘俊霞，等. 不同泌乳期奶山羊乳腺OPN基因表达及其对MCF-7细胞生长的影响[J]. 遗传， 2009， 31(8)：825-830.
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5.	Siiteri JE， Ensrud KM， Moore A， et al. Identification of osteopontin (OPN) mRNA and protein in the rat testis and epididymis， and on sperm[J]. Mol Reprod Dev， 1995， 40(1)：16-28.
6.	Liaw L， Lindner V， Schwartz SM， et al. Osteopontin and beta 3 integrin are coordinately expressed in regenerating endothelium in vivo and stimulate Arg-Gly-Asp-dependent endothelial migration in vitro[J]. Circ Res， 1995， 77(4)：665-672.
7.	Rudland PS， Platt-Higgins A， El-Tanani M， et al. Prognostic signi-ficance of the metastasis-associated protein osteopontin in human breast cancer[J]. Cancer Res， 2002， 62(12)：3417-3427.
8.	Chen L， Zhang JJ， Rafii S， et al. Suppression of tumor angiogenesis by Gα13 haploinsufficiency[J]. J Biol Chem， 2009， 284(40)：27409-27415.
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10.	Pardali E， ten Dijke P. Transforming growth factor-beta signalingand tumor angiogenesis[J]. Front Biosci， 2009， 14：4848-4861.
11.	Patani N， Jouhra F， Jiang W， et al. Osteopontin expression profiles predict pathological and clinical outcome in breast cancer[J]. Anticancer Res， 2008， 28(6B)：4105-4110.
12.	Yeatman TJ， Chambers AF. Osteopontin and colon cancer prog-ression[J]. Clin Exp Metastasis， 2003， 20(1)：85-90.
13.	Suzuki M， Mose E， Galloy C， et al. Osteopontin gene expressiondetermines spontaneous metastatic performance of orthotopic humanbreast cancer xenografts[J]. Am J Pathol， 2007， 171(2)：682-692.
14.	Brooks PC， Montgomery AM， Rosenfeld M， et al. Integrin ανβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels[J]. Cell， 1994， 79(7)：1157-1164.
15.	Roybal CN， Yang S， Sun CW， et al. Homocysteine increases the expression of vascular endothelial growth factor by a mechanism involving endoplasmic reticulum stress and transcription factor ATF4[J]. J Biol Chem， 2004， 279(15)：14844-14852.
16.	Chakraborty G， Jain S， Kundu GC. Osteopontin promotes vascularendothelial growth factor-dependent breast tumor growth and angi-ogenesis via autocrine and paracrine mechanisms[J]. Cancer Res， 2008， 68(1)：152-161.
17.	D’Amore M， Fanelli M， D’Amore S， et al. Receptor activator of NFκB ligand/osteoprotegerin (RANKL/OPG) system and osteopontin (OPN) serum levels in a population of apulian postmenopausal women[J]. Panminerva Med， 2006， 48(4)：215-221.
18.	Malyankar UM， Scatena M， Suchland KL， et al. Osteoprotegerin is an αvβ3-induced， NF-κB-dependent survival factor forendothelial cells[J]. J Biol Chem， 2000， 275(28)：20959-20962.
19.	Castronovo V， Bellahcene A. Evidence that breast cancer associated microcalcifications are mineralized malignant cells[J]. Int J Oncol， 1998， 12(2)：305-308.
20.	Oyama T， Sano T， Hikino T， et al. Microcalcifications of breast cancer and atypical cystic lobules associated with infiltration of foam cells expressing osteopontin[J]. Virchows Arch， 2002， 440(3)：267-273.

1. Siegel R， Naishadham D， Jemal A. Cancer statistics， 2012[J]. CA Cancer J Clin， 2012， 62(1)：10-29.
2. 孙杰，罗军，刘俊霞，等. 不同泌乳期奶山羊乳腺OPN基因表达及其对MCF-7细胞生长的影响[J]. 遗传， 2009， 31(8)：825-830.
3. Liu QF， Yu HW， Liu GN. Egr-1 upregulates OPN through direct binding to its promoter and OPN upregulates Egr-1 via the ERK pathway[J]. Mol Cell Biochem， 2009， 332(1-2)：77-84.
4. Young MF， Kerr JM， Termine JD， et al. cDNA cloning， mRNA distribution and heterogeneity， chromosomal location， and RFLP analysis of human osteopontin (OPN)[J]. Genomics， 1990， 7(4)：491-502.
5. Siiteri JE， Ensrud KM， Moore A， et al. Identification of osteopontin (OPN) mRNA and protein in the rat testis and epididymis， and on sperm[J]. Mol Reprod Dev， 1995， 40(1)：16-28.
6. Liaw L， Lindner V， Schwartz SM， et al. Osteopontin and beta 3 integrin are coordinately expressed in regenerating endothelium in vivo and stimulate Arg-Gly-Asp-dependent endothelial migration in vitro[J]. Circ Res， 1995， 77(4)：665-672.
7. Rudland PS， Platt-Higgins A， El-Tanani M， et al. Prognostic signi-ficance of the metastasis-associated protein osteopontin in human breast cancer[J]. Cancer Res， 2002， 62(12)：3417-3427.
8. Chen L， Zhang JJ， Rafii S， et al. Suppression of tumor angiogenesis by Gα13 haploinsufficiency[J]. J Biol Chem， 2009， 284(40)：27409-27415.
9. Gaur P， Bose D， Samuel S， et al. Targeting tumor angiogenesis[J]. Semin Oncol， 2009， 36(2 Suppl 1)：S12-S19.
10. Pardali E， ten Dijke P. Transforming growth factor-beta signalingand tumor angiogenesis[J]. Front Biosci， 2009， 14：4848-4861.
11. Patani N， Jouhra F， Jiang W， et al. Osteopontin expression profiles predict pathological and clinical outcome in breast cancer[J]. Anticancer Res， 2008， 28(6B)：4105-4110.
12. Yeatman TJ， Chambers AF. Osteopontin and colon cancer prog-ression[J]. Clin Exp Metastasis， 2003， 20(1)：85-90.
13. Suzuki M， Mose E， Galloy C， et al. Osteopontin gene expressiondetermines spontaneous metastatic performance of orthotopic humanbreast cancer xenografts[J]. Am J Pathol， 2007， 171(2)：682-692.
14. Brooks PC， Montgomery AM， Rosenfeld M， et al. Integrin ανβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels[J]. Cell， 1994， 79(7)：1157-1164.
15. Roybal CN， Yang S， Sun CW， et al. Homocysteine increases the expression of vascular endothelial growth factor by a mechanism involving endoplasmic reticulum stress and transcription factor ATF4[J]. J Biol Chem， 2004， 279(15)：14844-14852.
16. Chakraborty G， Jain S， Kundu GC. Osteopontin promotes vascularendothelial growth factor-dependent breast tumor growth and angi-ogenesis via autocrine and paracrine mechanisms[J]. Cancer Res， 2008， 68(1)：152-161.
17. D’Amore M， Fanelli M， D’Amore S， et al. Receptor activator of NFκB ligand/osteoprotegerin (RANKL/OPG) system and osteopontin (OPN) serum levels in a population of apulian postmenopausal women[J]. Panminerva Med， 2006， 48(4)：215-221.
18. Malyankar UM， Scatena M， Suchland KL， et al. Osteoprotegerin is an αvβ3-induced， NF-κB-dependent survival factor forendothelial cells[J]. J Biol Chem， 2000， 275(28)：20959-20962.
19. Castronovo V， Bellahcene A. Evidence that breast cancer associated microcalcifications are mineralized malignant cells[J]. Int J Oncol， 1998， 12(2)：305-308.
20. Oyama T， Sano T， Hikino T， et al. Microcalcifications of breast cancer and atypical cystic lobules associated with infiltration of foam cells expressing osteopontin[J]. Virchows Arch， 2002， 440(3)：267-273.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expressions of Osteopontin and Related Factors in Breast Cancer Tissues and Its Clinical Significance

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