Osteoplastic bone metastasis

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X-ray of the abdomen and pelvis of a 70-year-old patient with advanced prostate cancer. The increase in bone density due to the osteoplastic bone metastases (weaker blackening due to the lower transparency for the X-rays) is clearly visible.

Osteoplastic bone metastases are less common than the osteolytic variant . Their share in bone metastases is around 15%. Osteoplastic metastases mainly occur in prostate cancer, less often in other cancers. In the literature, osteoplastic metastases have been described in breast cancer, myeloma , colorectal carcinoma, astrocytoma , glioblastoma , thymoma , carcinoid , nasopharyngeal carcinoma, Zollinger-Ellison syndrome , leptomeningeal gliomatosis and cervical carcinoma .

Endothelin-1

Rod model of endothelin-1

The peptide hormone endothelin -1 (ET-1) seems to play a central role in osteoplastic metastases . The signaling pathways of ET-1 are not yet fully understood. It is found in osteocytes , osteoblasts , osteoclasts, and endothelial cells . In the osteoblasts that express the two endothelin receptors ET A and ET B , it stimulates mitosis (cell division). It also stimulates the formation of other bone growth factors such as BMP-7 ( bone morphogenetic protein 7 ). The transport of phosphate is of great importance for the structure of the bone matrix ( calcification ). Endothelin-1 activates the enzyme protein kinase C via the ET A receptor in the osteoblasts .

Tumors with osteoplastic metastases, such as prostate cancer and some forms of breast cancer , express endothelin-1 and the endothelin receptors. Therefore, it is assumed that the produced by the tumors endothelin-1 paracrine (the secreted factors act in the immediate environment of the cell) and / or autocrine (the secreted factors act on the cell itself) Effects with regard to the tumor growth and apoptosis has . In addition to endothelin-1, the epithelium of the prostate also produces the two endothelin receptors that are present throughout the gland. The plasma concentration of endothelin-1 is significantly higher in patients with advanced bone metastatic hormone-resistant prostate cancer than in patients with non-metastatic prostate cancer. The production of endothelin-1 is androgens downregulated and by factors such as TGF-β, epidermal growth factor ( epidermal growth factor , EGF), interleukin-1α , interleukin-1β and TNF-α up-regulated. In in-vitro experiments with prostate cancer cells and pieces of bone in coculture it was possible to show that the expression of endothelin-1 by the cancer cells is increased upon contact with the bone tissue. In the animal model of the nude mouse , a blockade of TGF-β can reduce the probability of metastasis of prostate cancer cells in the skeletal system.

Individual evidence

  1. ↑ S. Braun: Surgical therapy and prognosis in patients with skeletal carcinoma metastases. Dissertation, Ludwig Maximilians University of Munich, 2004.
  2. ↑ TA Guise, GR Mundy: Cancer and bone. In: Endocrine reviews Volume 19, Number 1, February 1998, pp. 18-54, ISSN  0163-769X . PMID 9494779 . (Review).
  3. ^ Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 29-1972. In: The New England journal of medicine Volume 287, Number 3, July 1972, pp. 138-143, ISSN  0028-4793 . doi : 10.1056 / NEJM197207202870308 . PMID 4338086 .
  4. ^ MR Paling, TL Pope: Computed tomography of isolated osteoblastic colon metastases in the bony pelvis. In: The Journal of computed tomography Volume 12, Number 3, July 1988, pp. 203-207, ISSN  0149-936X . PMID 3168541 .
  5. ^ JE Kingston, PN Plowman, BF Smith, NJ Garvan: Differentiated astrocytoma with osteoblastic skeletal metastases in a child. In: Child's nervous system Volume 2, Number 4, 1986, pp. 219-221, ISSN  0256-7040 . PMID 3779686 .
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  7. ↑ MK McLennan: Case report 657: Malignant epithelial thymoma with osteoplastic metastases. In: Skeletal radiology Volume 20, Number 2, 1991, pp. 141-144, ISSN  0364-2348 . PMID 2020863 .
  8. ^ N. Giordano, P. Nardi, P. Vigni, F. Palumbo, E. Battisti, C. Gennari: Osteoblastic metastases from carcinoid tumor. In: Clinical and Experimental Rheumatology Volume 12, Number 2, 1994 Mar-Apr, pp 228-229, ISSN  0392-856X . PMID 8039297 .
  9. ↑ CC Liaw, YS Ho, NG Koon-Kwan, TL Chen, WC Tzann: Nasopharyngeal carcinoma with brain metastasis: a case report. In: Journal of Neuro-Oncology Volume 22, Number 3, 1994, pp. 227-230, ISSN  0167-594X . PMID 7760099 .
  10. Jump up ↑ RT Pederson, DJ Haidak, RA Ferris, JS Macdonald, PS Schein: Osteoblastic bone metastasis in Zollinger-Ellison syndrome. In: Radiology Volume 118, Number 1, January 1976, pp. 63-64, ISSN  0033-8419 . PMID 1244675 .
  11. Jump up ↑ A. Pingi, G. Trasimeni, C. Di Biasi, G. Gualdi, G. Piazza, F. Corsi, F. Chiappetta: Diffuse leptomeningeal gliomatosis with osteoblastic metastases and no evidence of intraaxial lesions. In: AJNR. American journal of neuroradiology Volume 16, Number 5, May 1995, pp. 1018-1020, ISSN  0195-6108 . PMID 7639122 .
  12. ^ J. George, FM Lai: Metastatic cervical carcinoma presenting as psoas abscess and osteoblastic and lytic bony metastases. In: Singapore medical journal Volume 36, Number 2, April 1995, pp. 224-227, ISSN  0037-5675 . PMID 7676275 .
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  14. ↑ a b Y. Takuwa, T. Masaki, K. Yamashita: The effects of the endothelin family peptides on cultured osteoblastic cells from rat calvariae. In: Biochemical and biophysical research communications Volume 170, Number 3, August 1990, pp. 998-1005, ISSN  0006-291X . PMID 2202304 .
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  16. ↑ T. Sasaki, MH Hong: Endothelin-1 localization in bone cells and vascular endothelial cells in rat bone marrow. In: The Anatomical Record Volume 237, Number 3, November 1993, pp. 332-337, ISSN  0003-276X . doi : 10.1002 / ar.1092370306 . PMID 8291686 .
  17. ↑ PH Stern, A. Tatrai, DE Semler, SK Lee, P. Lakatos, PJ Strieleman, G. Tarjan, JL Sanders: Endothelin receptors, second messengers, and actions in bone. In: The Journal of Nutrition Volume 125, Number 7 Suppl, July 1995, pp. 2028S-2032S, ISSN  0022-3166 . PMID 7602388 . (Review).
  18. ↑ AM Kitten, CJ Andrews: Endothelin-1 expression in long-term cultures of fetal rat calvarial osteoblasts: regulation by BMP-7. In: Journal of Cellular Physiology Volume 187, Number 2, May 2001, pp. 218-225, ISSN  0021-9541 . doi : 10.1002 / jcp.1072 . PMID 11268001 .
  19. ↑ AM Kitten, SA Harvey, N. Criscimagna, M. Asher, JC Lee, MS Olson: Osteogenic protein-1 downregulates endothelin A receptors in primary rat osteoblasts. In: American Journal of Physiology-Endocrinology and Metabolism . 1997; 272: E967-E975, PMID 9227439 .
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  23. ↑ a b J. B. Nelson, SH Nguyen, JR Wu-Wong, TJ Opgenorth, DB Dixon, LW Chung, N. Inoue: New bone formation in an osteoblastic tumor model is increased by endothelin-1 overexpression and decreased by endothelin A receptor blockade. In: Urology Volume 53, Number 5, May 1999, pp. 1063-1069, ISSN  0090-4295 . PMID 10223507 .
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  25. ↑ JW Chiao, BS Moonga, YM Yang, R. Kancherla, A. Mittelman, JR Wu-Wong, T. Ahmed: Endothelin-1 from prostate cancer cells is enhanced by bone contact which blocks osteoclastic bone resorption. In: British journal of cancer Volume 83, Number 3, August 2000, pp. 360-365, ISSN  0007-0920 . doi : 10.1054 / bjoc.2000.1261 . PMID 10917552 . PMC 2374574 (free full text).
  26. Jump up ↑ S. Mishra, Y. Tang, L. Wang, L. Degraffenried, IT Yeh, S. Werner, D. Troyer, JA Copland, LZ Sun: Blockade of transforming growth factor-beta (TGFβ) signaling inhibits osteoblastic tumorigenesis by a novel human prostate cancer cell line. In: The Prostate [electronic publication before print] February 2011, ISSN  1097-0045 . doi : 10.1002 / pros.21361 . PMID 21321980 .