骨橋蛋白對腫瘤細胞惡性行為影響的研究進展_West China Medical Journal

Authors：

王傲立 , 宋關斌 ,  羅慶

重慶大學生物流變科學與技術教育部重點實驗室（重慶 400044）;

Corresponding?author：

羅慶, Email: qing.luo@cqu.edu.cn

Keywords：

骨橋蛋白; 腫瘤; 凋亡; 血管生成; 干性表型; 侵襲

DOI：

10.7507/1002-0179.201601145

Video：

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Abstract Full text Figures/Tables Video References Cited by

骨橋蛋白（osteopontin，OPN）是在多種組織中廣泛存在的一種分泌型糖蛋白，與癌癥的發生和進程有密切的關系，是癌癥的標志物之一。腫瘤細胞的惡性行為直接影響癌癥的治療和預后，近年來相關研究發現，OPN 以多種方式促進腫瘤細胞惡性行為。研究 OPN 對腫瘤細胞抗凋亡、血管生成、侵襲、干性維持等惡性行為的影響以及 OPN 在癌癥中的診斷意義，有利于為基于 OPN 的針對性治療方案的提出而提供理論參考。因此，該文從表型、分子機制和診斷意義幾個方面討論 OPN 對腫瘤細胞惡性行為的影響。

Citation： 王傲立, 宋關斌, 羅慶. 骨橋蛋白對腫瘤細胞惡性行為影響的研究進展. West China Medical Journal, 2017, 32(12): 1963-1966. doi: 10.7507/1002-0179.201601145 Copy

1.	Eyler CE, Rich JN. Survival of the fittest: cancer stem cells in therapeutic resistance and angiogenesis. J Clin Oncol, 2008, 26(17): 2839-2845.
2.	Liu Y, Gu X, Lin Q, et al. Prognostic significance of osteopontin in patients with non-small cell lung cancer: results from a meta-analysis. Int J Clin Exp Med, 2015, 8(8): 12765-12773.
3.	Bramwell VH, Tuck AB, Chapman JA, et al. Assessment of osteopontin in early breast cancer: correlative study in a randomised clinical trial. Breast Cancer Res, 2014, 16(1): R8.
4.	Johnson GA, Burghardt RC, Bazer FW. Osteopontin: a leading candidate adhesion molecule for implantation in pigs and sheep. J Anim Sci Biotechnol, 2014, 5(1): 56.
5.	Wang KX, Denhardt DT. Osteopontin: role in immune regulation and stress response. Cytokine Growth Factor Rev, 2008, 19(5-6): 333-345.
6.	Rittling SR, Singh R. Osteopontin in immune-mediated diseases. J Dent Res, 2015, 94(12): 1638-1645.
7.	Cao DX, Li ZJ, Jiang XO, et al. Osteopontin as potential biomarker and therapeutic target in gastric and liver cancers. World J Gastroenterol, 2012, 18(30): 3923-3930.
8.	Chae S, Jun HO, Lee EG, et al. Osteopontin splice variants differentially modulate the migratory activity of hepatocellular carcinoma cell lines. Int J Oncol, 2009, 35(6): 1409-1416.
9.	Tang XJ, Li JF, Yu BQ, et al. Osteopontin splice variants differentially exert clinicopathological features and biological functions in gastric cancer. Int J Biol Sci, 2013, 9(1): 55-66.
10.	Fong YC, Liu SC, Huang CY, et al. Osteopontin increases lung cancer cells migration via activation of the alphavbeta 3 integrin/FAK/Akt and NF-kappaB-dependent pathway. Lung Cancer, 2009, 64(3): 263-270.
11.	Hiraga T, Ito S, Nakamura H. Cancer stem-like cell marker CD44 promotes bone metastases by enhancing tumorigenicity, cell motility, and hyaluronan production. Cancer Res, 2013, 73(13): 4112-4122.
12.	Zhang H, Guo M, Chen JH, et al. Osteopontin knockdown inhibits av, β3 integrin-induced cell migration and invasion and promotes apoptosis of breast cancer cells by inducing autophagy and inactivating the PI3K/Akt/m TOR pathway. Cell Physiol Biochem, 2014, 33(4): 991-1002.
13.	Hsu KH, Tsai HW, Lin PW, et al. Anti-apoptotic effects of osteopontin through the up-regulation of Mcl-1 in gastrointestinal stromal tumors. World J Surg Oncol, 2014, 12: 189.
14.	Wu Y, Jiang W, Wang Y, et al. Breast cancer metastasis suppressor 1 regulates hepatocellular carcinoma cell apoptosis via suppressing osteopontin expression. PLoS One, 2012, 7(8): e42976.
15.	Dai J, Peng L, Fan K, et al. Osteopontin induces angiogenesis through activation of PI3K/AKT and ERK1/2 in endothelial cells. Oncogene, 2009, 28(38): 3412-3422.
16.	Chakraborty G, Jain S, Kundu GC. Osteopontin promotes vascular endothelial growth factor-dependent breast tumor growth and angiogenesis via autocrine and paracrine mechanisms. Cancer Res, 2008, 68(1): 152-161.
17.	Wu XL, Lin KJ, Bai AP, et al. Osteopontin knockdown suppresses the growth and angiogenesis of colon cancer cells. World J Gastroenterol, 2014, 20(30): 10440-10448.
18.	Wang Y, Yan W, Lu X, et al. Overexpression of osteopontin induces angiogenesis of endothelial progenitor cells via the avβ3/PI3K/AKT/eNOS/NO signaling pathway in glioma cells. Eur J Cell Biol, 2011, 90(8): 642-648.
19.	Kale S, Raja R, Thorat D, et al. Osteopontin signaling upregulates cyclooxygenase-2 expression in tumor-associated macrophages leading to enhanced angiogenesis and melanoma growth via α9β1 integrin. Oncogene. 2015, 34(42): 5408-5410.
20.	DeLisser HM. CD44: target for antiangiogenesis therapy. Blood, 2009, 114(25): 5114-5115.
21.	Sherwood DR. Cell invasion through basement membranes: an anchor of understanding. Trends Cell Biol, 2006, 16(5): 250-256.
22.	Song G, Ouyang G, Mao Y, et al. Osteopontin promotes gastric cancer metastasis by augmenting cell survival and invasion through Akt-mediated HIF-1alpha up-regulation and MMP9 activation. J Cell Mol Med, 2009, 13(8B): 1706-1718.
23.	Sun BS, You J, Li Y, et al. Osteopontin knockdown suppresses non-small cell lung cancer cell invasion and metastasis. Chin Med J (Engl). 2013, 126(9): 1683-1688.
24.	Gialeli C, Theocharis AD, Karamanos NK. Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. FEBS J, 2011, 278(1): 16-27.
25.	Chen YJ, Wei YY, Chen HT, et al. Osteopontin increases migration and MMP-9 up-regulation via alphavbeta3 integrin, FAK, ERK, and NF-kappaB-dependent pathway in human chondrosarcoma cells. J Cell Physiol, 2009, 221(1): 98-108.
26.	Behera R, Kumar V, Lohite K, et al. Activation of JAK2/STAT3 signaling by osteopontin promotes tumor growth in human breast cancer cells. Carcinogenesis, 2010, 31(2): 192-200.
27.	Liu H, Chen AM, Guo FJ, et al. A short-hairpin RNA targeting osteopontin downregulates MMP-2 and MMP-9 expressions in prostate cancer PC-3 cells. Cancer Lett, 2010, 295(1): 27-37.
28.	Zhang R, Pan X, Huang Z, et al. Osteopontin enhances the expression and activity of MMP-2 via the SDF-1/CXCR4 axis in hepatocellular carcinoma cell lines. PLoS One, 2011, 6(8): e23831.
29.	Duffy MJ, McGowan PM, Harbeck N, et al. uPA and PAI-1 as biomarkers in breast cancer: validated for clinical use in level-of-evidence-1 studies. Breast Cancer Res, 2014, 16(4): 428.
30.	Tang L, Han X. The urokinase plasminogen activator system in breast cancer invasion and metastasis. Biomed Pharmacother. 2013, 67(2): 179-182.
31.	Mi ZY, Guo HT, Wai PY, et al. Integrin-linked kinase regulates osteopontin-dependent MMP-2 and uPA expression to convey metastatic function in murine mammary epithelial cancer cells. Carcinogenesis, 2006, 27(6): 1134-1145.
32.	Das R, Mahabeleshwar GH, Kundu GC. Osteopontin stimulates cell motility and nuclear factor kappaB-mediated secretion of urokinase type plasminogen activator through phosphatidylinositol 3-kinase/Akt signaling pathways in breast cancer cells. J Biol Chem, 2003, 278(31): 28593-28606.
33.	Chen RX, Xia YH, Xue TC, et al. Osteopontin promotes hepatocellular carcinoma invasion by up-regulating MMP-2 and uPA expression. Mol Biol Rep, 2011, 38(6): 3671-3677.
34.	Lathia JD, Mack SC, Mulkearns-Hubert EE, et al. Cancer stem cells in glioblastoma. Genes Dev, 2015, 29(12): 1203-1217.
35.	Lamour V, Henry A, Kroonen J, et al. Targeting osteopontin suppresses glioblastoma stem-like cell character and tumorigenicity in vivo. Int J Cancer, 2015, 137(5): 1047-1057.
36.	Ng L, Wan T, Chow A, et al. Osteopontin overexpression induced tumor progression and chemoresistance to oxaliplatin through induction of stem-like properties in human colorectal cancer. Stem Cells Int, 2015, 2015: 247892.
37.	Cao L, Fan X, Jing W, et al. Osteopontin promotes a cancer stem cell-like phenotype in hepatocellular carcinoma cells via an integrin-NF-κB-HIF-1α pathway. Oncotarget, 2015, 6(9): 6627-6640.
38.	Li ZZ, Bao S, Wu QL, et al. Hypoxia-Inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell, 2009, 15(6): 501-513.
39.	Semenza GL. Regulation of the breast cancer stem cell phenotype by hypoxia-inducible factors. Clin Sci, 2015, 129(12): 1037-1045.
40.	Pietras A, Katz AM, Ekstr?m EJ, et al. Osteopontin-CD44 signaling in the glioma perivascular niche enhances cancer stem cell phenotypes and promotes aggressive tumor growth. Cell Stem Cell, 2014, 14(3): 357-369.
41.	Iqbal J, Mcrae S, Banaudha K, et al. Mechanism of hepatitis C virus (HCV)-induced osteopontin and its role in epithelial to mesenchymal transition of hepatocytes. J Biol Chem, 2013, 288(52): 36994-37009.
42.	Takafuji V, Forgues M, Unsworth E, et al. An osteopontin fragment is essential for tumor cell invasion in hepatocellular carcinoma. Oncogene, 2007, 26(44): 6361-6371.
43.	Tilli TM, Mello KD, Ferreira LB, et al. Both osteopontin-c and osteopontin-b splicing isoforms exert pro-tumorigenic roles in prostate cancer cells. Prostate, 2012, 72(15): 1688-1699.
44.	Hartung F, Weber GF. RNA blood levels of osteopontin splice variants are cancer markers. Springerplus, 2013, 2(1): 110.
45.	Zduniak K, Ziolkowski P, Ahlin C, et al. Nuclear osteopontin-c is a prognostic breast cancer marker. Br J Cancer, 2015, 112(4): 729-738.

1. Eyler CE, Rich JN. Survival of the fittest: cancer stem cells in therapeutic resistance and angiogenesis. J Clin Oncol, 2008, 26(17): 2839-2845.
2. Liu Y, Gu X, Lin Q, et al. Prognostic significance of osteopontin in patients with non-small cell lung cancer: results from a meta-analysis. Int J Clin Exp Med, 2015, 8(8): 12765-12773.
3. Bramwell VH, Tuck AB, Chapman JA, et al. Assessment of osteopontin in early breast cancer: correlative study in a randomised clinical trial. Breast Cancer Res, 2014, 16(1): R8.
4. Johnson GA, Burghardt RC, Bazer FW. Osteopontin: a leading candidate adhesion molecule for implantation in pigs and sheep. J Anim Sci Biotechnol, 2014, 5(1): 56.
5. Wang KX, Denhardt DT. Osteopontin: role in immune regulation and stress response. Cytokine Growth Factor Rev, 2008, 19(5-6): 333-345.
6. Rittling SR, Singh R. Osteopontin in immune-mediated diseases. J Dent Res, 2015, 94(12): 1638-1645.
7. Cao DX, Li ZJ, Jiang XO, et al. Osteopontin as potential biomarker and therapeutic target in gastric and liver cancers. World J Gastroenterol, 2012, 18(30): 3923-3930.
8. Chae S, Jun HO, Lee EG, et al. Osteopontin splice variants differentially modulate the migratory activity of hepatocellular carcinoma cell lines. Int J Oncol, 2009, 35(6): 1409-1416.
9. Tang XJ, Li JF, Yu BQ, et al. Osteopontin splice variants differentially exert clinicopathological features and biological functions in gastric cancer. Int J Biol Sci, 2013, 9(1): 55-66.
10. Fong YC, Liu SC, Huang CY, et al. Osteopontin increases lung cancer cells migration via activation of the alphavbeta 3 integrin/FAK/Akt and NF-kappaB-dependent pathway. Lung Cancer, 2009, 64(3): 263-270.
11. Hiraga T, Ito S, Nakamura H. Cancer stem-like cell marker CD44 promotes bone metastases by enhancing tumorigenicity, cell motility, and hyaluronan production. Cancer Res, 2013, 73(13): 4112-4122.
12. Zhang H, Guo M, Chen JH, et al. Osteopontin knockdown inhibits av, β3 integrin-induced cell migration and invasion and promotes apoptosis of breast cancer cells by inducing autophagy and inactivating the PI3K/Akt/m TOR pathway. Cell Physiol Biochem, 2014, 33(4): 991-1002.
13. Hsu KH, Tsai HW, Lin PW, et al. Anti-apoptotic effects of osteopontin through the up-regulation of Mcl-1 in gastrointestinal stromal tumors. World J Surg Oncol, 2014, 12: 189.
14. Wu Y, Jiang W, Wang Y, et al. Breast cancer metastasis suppressor 1 regulates hepatocellular carcinoma cell apoptosis via suppressing osteopontin expression. PLoS One, 2012, 7(8): e42976.
15. Dai J, Peng L, Fan K, et al. Osteopontin induces angiogenesis through activation of PI3K/AKT and ERK1/2 in endothelial cells. Oncogene, 2009, 28(38): 3412-3422.
16. Chakraborty G, Jain S, Kundu GC. Osteopontin promotes vascular endothelial growth factor-dependent breast tumor growth and angiogenesis via autocrine and paracrine mechanisms. Cancer Res, 2008, 68(1): 152-161.
17. Wu XL, Lin KJ, Bai AP, et al. Osteopontin knockdown suppresses the growth and angiogenesis of colon cancer cells. World J Gastroenterol, 2014, 20(30): 10440-10448.
18. Wang Y, Yan W, Lu X, et al. Overexpression of osteopontin induces angiogenesis of endothelial progenitor cells via the avβ3/PI3K/AKT/eNOS/NO signaling pathway in glioma cells. Eur J Cell Biol, 2011, 90(8): 642-648.
19. Kale S, Raja R, Thorat D, et al. Osteopontin signaling upregulates cyclooxygenase-2 expression in tumor-associated macrophages leading to enhanced angiogenesis and melanoma growth via α9β1 integrin. Oncogene. 2015, 34(42): 5408-5410.
20. DeLisser HM. CD44: target for antiangiogenesis therapy. Blood, 2009, 114(25): 5114-5115.
21. Sherwood DR. Cell invasion through basement membranes: an anchor of understanding. Trends Cell Biol, 2006, 16(5): 250-256.
22. Song G, Ouyang G, Mao Y, et al. Osteopontin promotes gastric cancer metastasis by augmenting cell survival and invasion through Akt-mediated HIF-1alpha up-regulation and MMP9 activation. J Cell Mol Med, 2009, 13(8B): 1706-1718.
23. Sun BS, You J, Li Y, et al. Osteopontin knockdown suppresses non-small cell lung cancer cell invasion and metastasis. Chin Med J (Engl). 2013, 126(9): 1683-1688.
24. Gialeli C, Theocharis AD, Karamanos NK. Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. FEBS J, 2011, 278(1): 16-27.
25. Chen YJ, Wei YY, Chen HT, et al. Osteopontin increases migration and MMP-9 up-regulation via alphavbeta3 integrin, FAK, ERK, and NF-kappaB-dependent pathway in human chondrosarcoma cells. J Cell Physiol, 2009, 221(1): 98-108.
26. Behera R, Kumar V, Lohite K, et al. Activation of JAK2/STAT3 signaling by osteopontin promotes tumor growth in human breast cancer cells. Carcinogenesis, 2010, 31(2): 192-200.
27. Liu H, Chen AM, Guo FJ, et al. A short-hairpin RNA targeting osteopontin downregulates MMP-2 and MMP-9 expressions in prostate cancer PC-3 cells. Cancer Lett, 2010, 295(1): 27-37.
28. Zhang R, Pan X, Huang Z, et al. Osteopontin enhances the expression and activity of MMP-2 via the SDF-1/CXCR4 axis in hepatocellular carcinoma cell lines. PLoS One, 2011, 6(8): e23831.
29. Duffy MJ, McGowan PM, Harbeck N, et al. uPA and PAI-1 as biomarkers in breast cancer: validated for clinical use in level-of-evidence-1 studies. Breast Cancer Res, 2014, 16(4): 428.
30. Tang L, Han X. The urokinase plasminogen activator system in breast cancer invasion and metastasis. Biomed Pharmacother. 2013, 67(2): 179-182.
31. Mi ZY, Guo HT, Wai PY, et al. Integrin-linked kinase regulates osteopontin-dependent MMP-2 and uPA expression to convey metastatic function in murine mammary epithelial cancer cells. Carcinogenesis, 2006, 27(6): 1134-1145.
32. Das R, Mahabeleshwar GH, Kundu GC. Osteopontin stimulates cell motility and nuclear factor kappaB-mediated secretion of urokinase type plasminogen activator through phosphatidylinositol 3-kinase/Akt signaling pathways in breast cancer cells. J Biol Chem, 2003, 278(31): 28593-28606.
33. Chen RX, Xia YH, Xue TC, et al. Osteopontin promotes hepatocellular carcinoma invasion by up-regulating MMP-2 and uPA expression. Mol Biol Rep, 2011, 38(6): 3671-3677.
34. Lathia JD, Mack SC, Mulkearns-Hubert EE, et al. Cancer stem cells in glioblastoma. Genes Dev, 2015, 29(12): 1203-1217.
35. Lamour V, Henry A, Kroonen J, et al. Targeting osteopontin suppresses glioblastoma stem-like cell character and tumorigenicity in vivo. Int J Cancer, 2015, 137(5): 1047-1057.
36. Ng L, Wan T, Chow A, et al. Osteopontin overexpression induced tumor progression and chemoresistance to oxaliplatin through induction of stem-like properties in human colorectal cancer. Stem Cells Int, 2015, 2015: 247892.
37. Cao L, Fan X, Jing W, et al. Osteopontin promotes a cancer stem cell-like phenotype in hepatocellular carcinoma cells via an integrin-NF-κB-HIF-1α pathway. Oncotarget, 2015, 6(9): 6627-6640.
38. Li ZZ, Bao S, Wu QL, et al. Hypoxia-Inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell, 2009, 15(6): 501-513.
39. Semenza GL. Regulation of the breast cancer stem cell phenotype by hypoxia-inducible factors. Clin Sci, 2015, 129(12): 1037-1045.
40. Pietras A, Katz AM, Ekstr?m EJ, et al. Osteopontin-CD44 signaling in the glioma perivascular niche enhances cancer stem cell phenotypes and promotes aggressive tumor growth. Cell Stem Cell, 2014, 14(3): 357-369.
41. Iqbal J, Mcrae S, Banaudha K, et al. Mechanism of hepatitis C virus (HCV)-induced osteopontin and its role in epithelial to mesenchymal transition of hepatocytes. J Biol Chem, 2013, 288(52): 36994-37009.
42. Takafuji V, Forgues M, Unsworth E, et al. An osteopontin fragment is essential for tumor cell invasion in hepatocellular carcinoma. Oncogene, 2007, 26(44): 6361-6371.
43. Tilli TM, Mello KD, Ferreira LB, et al. Both osteopontin-c and osteopontin-b splicing isoforms exert pro-tumorigenic roles in prostate cancer cells. Prostate, 2012, 72(15): 1688-1699.
44. Hartung F, Weber GF. RNA blood levels of osteopontin splice variants are cancer markers. Springerplus, 2013, 2(1): 110.
45. Zduniak K, Ziolkowski P, Ahlin C, et al. Nuclear osteopontin-c is a prognostic breast cancer marker. Br J Cancer, 2015, 112(4): 729-738.

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骨橋蛋白對腫瘤細胞惡性行為影響的研究進展

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