Expression of bone morphogenetic proteins in human metastatic prostate and breast cancer.

AIM To analyze the expression of bone morphogenetic proteins (BMPs) in prostate and breast cancers with established metastasis in bone, where prostate cancer causes osteoblastic metastases, and breast cancer osteolytic metastases. METHODS Primary tumor specimens from 20 patients with prostate cancer and 15 with breast cancer were studied for BMP-2/4, -3, -5, -6 and -7 immunohistochemistry. All patients had multiple bone metastases proven by bone scan. We also examined BMPs expression in normal prostate and breast tissues. BMPs expression was compared with clinicopathological and biochemical parameters. RESULTS Cytoplasmic BMPs immunostaining was observed in both prostate cancer and normal prostate tissue. Expression of BMP-2/4, -5, -6, and -7 proteins was detected in all normal prostate samples, with the predominance of BMP-2/4 (87.8-/+11.4% positive cells) and BMP-7 (94.6-/+0.9% positive cells). In prostate cancer tissues, we found variable expression of all BMPs. BMP-2/4 (83-/+11.6% positive cells) was predominantly expressed in prostate carcinoma, whereas the expression of BMP-7 (24.3-/+19.2% positive cells) was significantly lower than in the normal prostate. In all breast cancers tissues, we found nuclear staining only for BMP-7. In normal breast tissue, the BMP expression was not detectable. The percent of BMP-7 positive cells in breast cancer (86.4-/+7.3%) was higher than in prostatic cancer. Comparing BMP expression levels and clinicopathological parameters, we did not find statistical difference, except for serum alkaline phosphatase, which was significantly higher in patients with prostate cancer. CONCLUSION The expression of BMPs differs between prostate and breast cancer cells. Identifying the BMP proteins in cancers may be useful for monitoring the tumor status with reference to metastases.

[1]  R. Walker,et al.  World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs , 2005 .

[2]  I. Sesterhenn,et al.  World health organization classifications of tumours. pathology and genetics of tumours of the urinary system and male genital organs , 2005 .

[3]  Seong-Jin Kim,et al.  Restoration of Bone Morphogenetic Protein Receptor Type II Expression Leads to a Decreased Rate of Tumor Growth in Bladder Transitional Cell Carcinoma Cell Line TSU-Pr1 , 2004, Cancer Research.

[4]  Hans Clevers,et al.  Signaling pathways in intestinal development and cancer. , 2004, Annual review of cell and developmental biology.

[5]  H. Yoshikawa,et al.  The expression and prognostic significance of bone morphogenetic protein-2 in patients with malignant fibrous histiocytoma. , 2004, The Journal of bone and joint surgery. British volume.

[6]  H. Yoshikawa,et al.  Bone morphogenetic proteins in bone tumors , 2004, Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association.

[7]  G. Roodman Mechanisms of bone metastasis. , 2004, Discovery medicine.

[8]  H. Yamanaka,et al.  Expression of bone morphogenetic protein‐7 (BMP‐7) in human prostate , 2004, The Prostate.

[9]  M. Nachtigal,et al.  Identification of a putative autocrine bone morphogenetic protein-signaling pathway in human ovarian surface epithelium and ovarian cancer cells. , 2003, Endocrinology.

[10]  J. Clement,et al.  Differential expression and regulation of bone morphogenetic protein 7 in breast cancer. , 2003, International journal of oncology.

[11]  M. Noguchi,et al.  Serum levels of bone turnover markers parallel the results of bone scintigraphy in monitoring bone activity of prostate cancer. , 2003, Urology.

[12]  H. Yamanaka,et al.  Increased expression of bone morphogenetic protein‐7 in bone metastatic prostate cancer , 2003, The Prostate.

[13]  F. Hamdy,et al.  Bone morphogenetic protein-6: potential mediator of osteoblastic metastases in prostate cancer , 2000, Prostate Cancer and Prostatic Diseases.

[14]  L. Sobin,et al.  World Health Organization classification of tumors , 2000, Cancer.

[15]  S. F. Arnold,et al.  Identification of bone morphogenetic proteins and their receptors in human breast cancer cell lines: importance of BMP2. , 1999, Cytokine.

[16]  M. Webber,et al.  Osteonectin promotes prostate cancer cell migration and invasion: a possible mechanism for metastasis to bone. , 1999, Cancer research.

[17]  L. Chung,et al.  Osteomimetic properties of prostate cancer cells: A hypothesis supporting the predilection of prostate cancer metastasis and growth in the bone environment , 1999, The Prostate.

[18]  J. Clement,et al.  Expression of bone morphogenetic protein 6 in normal mammary tissue and breast cancer cell lines and its regulation by epidermal growth factor , 1999, International journal of cancer.

[19]  F. Hamdy,et al.  Bone morphogenetic protein 6 in skeletal metastases from prostate cancer and other common human malignancies. , 1998, British Journal of Cancer.

[20]  M. Bolander,et al.  Evidence for the upregulation of osteogenic protein‐1 mRNA expression in musculoskeletal neoplasms , 1998, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[21]  Teruhiko Yoshida,et al.  Growth regulation of human prostate cancer cells by bone morphogenetic protein-2. , 1997, Cancer research.

[22]  F. Hamdy,et al.  Immunolocalization and messenger RNA expression of bone morphogenetic protein-6 in human benign and malignant prostatic tissue. , 1997, Cancer research.

[23]  T. Dale,et al.  Regulation of Msx-1, Msx-2, Bmp-2 and Bmp-4 during foetal and postnatal mammary gland development. , 1996, Development.

[24]  B. Hogan Bone morphogenetic proteins in development. , 1996, Current opinion in genetics & development.

[25]  H. Rao Bone morphogenetic protein-6 expression in normal and malignant prostate , 1996 .

[26]  R. Dickson,et al.  Growth factors in breast cancer. , 1995, Endocrine reviews.

[27]  S. Pinder,et al.  Histological grading of breast carcinomas: a study of interobserver agreement. , 1995, Human pathology.

[28]  P. Kostenuik,et al.  Tumor-bone interactions in skeletal metastasis. , 1995, Clinical orthopaedics and related research.

[29]  J. Wozney,et al.  Expression of bone morphogenetic protein messenger RNAs by normal rat and human prostate and prostate cancer cells , 1994, The Prostate.

[30]  Subburaman Mohan,et al.  Growth factors to stimulate bone formation , 1993, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[31]  J. Ware,et al.  Growth factors and their receptors as determinants in the proliferation and metastasis of human prostate cancer , 1993, Cancer and Metastasis Reviews.

[32]  R. Russell,et al.  Expression of bone morphogenetic proteins in human prostatic adenocarcinoma and benign prostatic hyperplasia. , 1992, British Journal of Cancer.

[33]  J. Wozney,et al.  The bone morphogenetic protein family and osteogenesis , 1992, Molecular reproduction and development.

[34]  I. Ellis,et al.  Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. , 2002, Histopathology.

[35]  A. Reddi,et al.  Dissociative extraction and reconstitution of extracellular matrix components involved in local bone differentiation. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[36]  M. Urist,et al.  Bone: Formation by Autoinduction , 1965, Science.

[37]  J. Barnes,et al.  Bone morphogenetic protein-6 expression in normal and malignant prostate , 2004, World Journal of Urology.

[38]  Peter Devilee,et al.  Pathology and Genetics of Tumours of the Breast and Female Genital Organs , 2003 .

[39]  S. Vukicevic,et al.  Biology of bone morphogenetic proteins , 2002 .

[40]  S. Vukicevic,et al.  From laboratory to clinical practice , 2002 .

[41]  A. Reddi Bone morphogenetic proteins: from basic science to clinical applications. , 2001, The Journal of bone and joint surgery. American volume.

[42]  M. Harder IFCC METHODS FOR THE MEASUREMENT OF CATALYTIC CONCENTRATION OF ENZYMES , 1980 .