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Elevated Serum Periostin Levels in Patients with Bone Metastases from Breast but not Lung Cancer

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Abstract

Periostin is a recently identified gene that is preferentially expressed in periosteum, indicating a potential role in bone formation and maintenance of structure. We independently identified and isolated periostin from cancer tissue, using the palindromic PCR-driven cDNA Differential Display technique. For the present work, we developed a novel sandwich chemiluminescence assay to detect serum periostin level using newly developed monoclonal and polyclonal antibodies. We investigated serum periostin levels in breast cancer and small cell lung cancer patients, especially in patients with bone metastasis. The study included 58 breast cancer and 44 small cell lung cancer patients. Serum periostin levels were elevated in breast cancer patients presenting with bone metastases (92.0 ± 28.6 ng/ml) compared to similar breast cancer patients without evidence of bone metastasis (55.0 ± 16.6 ng/ml, p = 0.04). No correlation was found between the serum periostin level and any other prognostic factors, such as clinical stage and lymph node metastasis in breast cancer. Serum periostin levels thus appear to serve as a marker of bone metastasis from breast cancer. In contrast, serum periostin levels were similar in samples from patients with small cell lung cancer who did or did not have bone metastasis. However, increasing T-stage and N-stage of patients with small cell lung cancer were correlated with higher periostin levels (T4, 126.5 ± 29.7 ng/ml v.s. T2, 64.9 ± 16.1 ng/ml, p = 0.03; and T4 v.s. T1, 36.3 ± 7.5 ng/ml, p = 0.01; N3, 108.7 ± 17.3 ng/ml v.s. N2, 49.7 ± 10.9 ng/ml, p = 0.01). Periostin has a substantial homology with the insect cell adhesion molecule, fasciclin I. Thus, expression of periostin may facilitate tumor cell adhesion to the bone surface. In fact, we found by in situ RNA hybridization, that the periostin gene was highly expressed in the stromal cells immediately surrounding the tumor, but not within the breast cancer cells themselves.

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References

  1. Yoneda T: Cellular and molecular basis of preferential metastasis of breast cancer to bone. J Orthop Sci 5: 75-81, 2000

    Google Scholar 

  2. Glaslo CSB: Incidence and distribution of skeletal metastases. In: Glasko CSB (ed) Skeletal Metastases. Butterworth, London, 1986, pp 14-21

    Google Scholar 

  3. Rubens RD: The nature of metastatic bone disease. In: Rubens RD, Foglman I (eds) Bone Metastases. Diagnosis and Treatment. Springer, London, 1991, pp 1-10

    Google Scholar 

  4. Abram HL, Spiro R, Goldstein N: Metastasis in carcinomas: analysis of 1000 autopsied cases. Cancer 3: 74-85, 1950

    Google Scholar 

  5. Kraeft S-K, Sutherland R, Gravelin L, Hu G-H, Ferland LH, Richardson P, Elias A, Chen LB: Detection and analysis of cancer cells in blood and bone marrow using a rare event imaging system. Clin Cancer Res 6: 434-442, 2000

    Google Scholar 

  6. Bundred NJ, Walker RA, Ratcliffe WA, Warwick J, Morrison JM, Ratcliffe JG: Parathyroid hormone related protein and skeletal morbidity in breast cancer. Eur J Cancer 28: 690-692, 1992

    Google Scholar 

  7. Bellahcene A, Castronovo V: Expression of bone matrix proteins in human breast cancer: potential roles in microcalcification formation and in the genesis of bone metastases. B Cancer 84: 17-24, 1997

    Google Scholar 

  8. Bellahcene A, Maloujahmoum N, Fisher LW, Pastorino H, Tagliabue E, Menard S, Castronovo V: Expression of bone sialoprotein in human lung cancer. Calcified Tissue Int 61: 183-188, 1997

    Google Scholar 

  9. Coleman RE, Houston D, James I, Rodger A, Rubens RD, Leonard RCF, Ford J: Preliminary results of use of urinary excretion of pyridinium crosslinks for monitoring metastatic disease. Brit J Cancer 65: 766-768, 1992

    Google Scholar 

  10. Blomqvist C, Risteli L, Virkkunen P, Sarna S, Elomaa I: Markers of type I collagen degradation and synthesis in the monitoring of treatment response in bone metastases from breast carcinoma. Brit J Cancer 73: 1074-1079, 1996

    Google Scholar 

  11. Koizumi M, Yamada Y, Takiguchi T, Nomura E, Furukawa M, Kitahara T, Yamashita T, Maeda H, Takahashi S, Aiba K, Ogata E: Bone metabolic markers in bone metastases. J Cancer Res Clin 121: 542-548, 1995

    Google Scholar 

  12. Aruga A, Koizumi M, Hotta R, Takahashi S, Ogata E: Usefulness of bone metabolic markers in the diagnosis and followup of bone metastasis from lung cancer. Brit J Cancer 76: 760-764, 1997

    Google Scholar 

  13. Takeshita S, Kikuno R, Tezuka K, Amann E: Osteoblastspecific factor 2: Cloning of a putative bone adhesion protein with homology with the insect protein fasciclin I. Biochem J 294: 271-278, 1993

    Google Scholar 

  14. Horiuchi K, Amizuka N, Takeshita S, Takamatsu H, Katsuura M, Ozawa H, Toyama Y, Bonewald L, Kudo A: Identification and characterization of a novel protein, periostin, with restricted expression to periosteum and periodontal ligament and increased expression by transforming growth factor-β. J Bone Miner Res 14: 1239-1249, 1999

    Google Scholar 

  15. LeBaron RG, Bezverkov KV, Zimber MP, Pavelec R, Skonier J, Purchio AF: βIGH3, a novel secretary protein inducible by transforming growth factor-β is present in normal skin and promotes the adhesion and spreading of dermal fibroblasts in vitro. J Invest Dermatol 104: 844-849, 1995

    Google Scholar 

  16. Skonier J, Neubauer M, Madisen L, Mbennett K, Plowman GD, Purchio AF: cDNA cloning and sequence analysis of βIGH3, a novel gene induced in a human adenocarcinoma cell line after treatment with transforming growth factor β. DNA Cell Biol 11: 511-522, 1992

    Google Scholar 

  17. Zinn K, McAllister L, Goodman CS: Sequence analysis and neuronal expression of fasciclin I in grasshopper and Drosophila. Cell 53: 577-687, 1988

    Google Scholar 

  18. Lal A, Lash AE, Altschul SF, Velculescu V, Zhang L, McLendon RE, Marra MA, Prange C, Mortin PJ, Polyak K, Papadopoulos N, Vogelstein B, Kinzler KW, Strausberg RL, Riggins GJ: A public database for gene expression in human cancers. Cancer Res 59: 5403-5407, 1999

    Google Scholar 

  19. Bao S, Chang MS, Auclair D, Sun Y, Wang Y, Wong WK, Zhang J, Liu Y, Qian X, Sutherland R, Magi GC, Weisberg E, Cheng EY, Hao L, Sasaki H, Campbell MS, Kraeft SK, Loda M, Lo KM, Chen LB: Hrad17, a human homologue of the Schizosaccharomyces pombe checkpoint gene rad17, is overexpressed in colon carcinoma. Cancer Res 59: 2023-2028, 1999

    Google Scholar 

  20. Sasaki H, Lo KM, Chen LB, Auclair D, Nakashima Y, Moriyama S, Fukai I, Tam C, Loda M, Fujii Y: Expression of periostin, homologous with an insect cell adhesion molecule as a prognostic marker in non-small cell lung cancers. Jpn J Cancer Res 92: 869-873, 2001

    Google Scholar 

  21. Sasaki H, Roberts J, Lykins D, Fujii Y, Auclair D, Chen LB: Novel chemiluminescence assay for serum periostin levels in women with preeclampsia and in normotensive pregnant women. Am J Obstet Gynecol 186: 103-108, 2002

    Google Scholar 

  22. Gunn MD, Tangemann K, Tam C, Cyster JG, Rosen SD, Williams LT: A chemokine expressed in lymphoid high endothelial venules promotes the adhesion and chemotaxis of native T lymphocytes. Proc Natl Acad Sci USA 95: 258-263, 1998

    Google Scholar 

  23. Suzuki S: Early diagnosis for bone metastasis of breast cancer based on bone metabolism. Fukushima J Med Sci 36: 11-27, 1990

    Google Scholar 

  24. Pfohler C, Fixemer T, Jung V, Dooley S, Remberger K, Bonkhoff H: In situ hybridization analysis of genes coding collagen IV alpha1 chain, laminin beta 1 chain, and S-laminin in prostate tissue and in prostate cancer: increased basement membrane gene expression high-grade and metastatic lesions. Prostate 136: 143-150, 1998

    Google Scholar 

  25. Mundy GR: Mechanisms of bone metastasis. Cancer 80: 1546-1556, 1997

    Google Scholar 

  26. Diel IJ, Solomayer E-F, Seibel MJ, Pfeilschifter J, Maisenbacher H, Gollan C, Pecherstorfer M, Conradi D, Kehr G, Boehm E, Armbruster FP, Bastert G: Serum bone sialoprotein in patients with primary breast cancer is a prognostic marker for subsequent bone metastasis. Clin Cancer Res 5: 3914-3919, 1999

    Google Scholar 

  27. Yin JJ, Spinks TJ, Chui Y, Dallas M, Guise TA: Clonal variation in parathyroid hormone-related protein (PTHrP) secretion by a human breast cancer cell line alter severity of osteolytic metastases. J Bone Miner Res 12(1): S107, 1997

    Google Scholar 

  28. Grill V, Ho P, Body JJ, Johanson N, Lee SC, Kukreja SC, Moseley JM, Martin TJ: Parathyroid related-protein: elevated levels in both humoral hypercalcemia and hypercalcemia complicating metastatic breast cancer. J Clin Endocr Metab 73: 1309-1315, 1991

    Google Scholar 

  29. Henderson M, Danks J, Moseley J, Slavin J, Harris T, McKinlay M, Hopper J, Martin T: Parathyroid hormonerelated protein production by breast cancers, improved survival, and reduced bone metastases. J Natl Cancer I 93: 234-237, 2001

    Google Scholar 

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Authors and Affiliations

  1. Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, MA, USA

    Hidefumi Sasaki, Chih-Yi Yu, Meiru Dai, Daniel Auclair & Lan Bo Chen

  2. Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, MA, USA

    Carmen Tam, Massimo Loda & Anthony Elias

  3. Department of Surgery II, Nagoya City University Medical School, Nagoya, Japan

    Hidefumi Sasaki

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  1. Hidefumi Sasaki
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  2. Chih-Yi Yu
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  3. Meiru Dai
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Sasaki, H., Yu, CY., Dai, M. et al. Elevated Serum Periostin Levels in Patients with Bone Metastases from Breast but not Lung Cancer. Breast Cancer Res Treat 77, 245–252 (2003). https://doi.org/10.1023/A:1021899904332

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