乳腺癌微钙化形成的分子机制

张瑜; 王文; 米成嵘

doi:10.3969/j.issn.1674-4500.2018.03.05

乳腺癌微钙化形成的分子机制

doi: 10.3969/j.issn.1674-4500.2018.03.05

张瑜^1,,
王文²,
米成嵘^3, ,

1.
宁夏医科大学临床医学院
2.
总医院心脑血管病医院超声科
3.
总医院超声科，宁夏银川 750000

详细信息

作者简介:
张瑜：张瑜，在读硕士研究生，E-mail: 45076457@qq.com

通讯作者:
米成嵘，主任医师，E-mail: mcr69333@163.com

计量
- 文章访问数: 2602
- HTML全文浏览量: 1014
- PDF下载量: 21
- 被引次数: 0
出版历程
- 收稿日期: 2018-04-28
- 刊出日期: 2018-07-01

Molecular mechanism of microcalcification in breast cancer

Yu ZHANG^1
,,
Wen WANG²,
Chengrong MI^{3
, ,}

1.
School of Clinical Medicine
2.
Department of Ultrasound,Cardio-cerebrovascular Disease Hospital affiliated to General Hospital
3.
Department of Ultrasound, General Hospital, Ningxia Medical University, Yinchuan 750000,China

摘要

摘要: 乳腺微钙化（MC）是乳腺癌重要的影像学特征。在乳腺组织中常见两种类型的MC物质，Ⅰ型MC（草酸钙）仅存在于良性病变中，而Ⅱ型MC（羟磷灰石）通常存在于恶性病变中。研究者们利用这一影像学特征制定和发明了先进的影像诊断程序和成像技术，然而MC形成的机制却了解甚少。因此，本文试图解释乳腺癌MC形成的分子机制，其重点在于部分异质性乳腺癌细胞如何获得成骨样表型并启动病理性钙化过程。同时，本文还强调了骨形成蛋白、肿瘤相关巨噬细胞以及上皮间质化过程在病理性钙化过程中的调控作用。
- 乳腺微钙化 /
- 分子机制 /
- 乳腺癌
Abstract: Breast microcalcification (MC) is an important imaging feature of breast cancer. There are two types of MC in the breast tissue; microcalcification type I (calcium oxalate) only occurs in benign lesions, whereas type II (calcium hydroxyapatite) generally in malignant lesions. Over the past few decades, researchers have formulated advanced imaging diagnostic procedures and imaging techniques based on this imaging feature, while the mechanism of its formation is still poorly understood. Hence, this paper attempts to address the molecular mechanism of microcalcification in breast cancer, with focus on how a subpopulation of heterogeneous breast tumor cells attains an osteoblast-like phenotype and activates pathophysiological microcalcification. Also, the regulatory effect of bone morphogenetic proteins, tumor-associated macrophages and epithelial-mesenchymal transition in this pathological calcification of breast has been highlighted.
- microcalcification in breast cancer /
- molecular mechanism /
- breast cancer

HTML全文

参考文献(45)

[1]	Desantis C, Siegel R, Bandi P, et al. Breast cancer statistics[J]. CA Cancer J Clin, 2011, 61(6): 409-18.
[2]	Bellahcene A, Castronovo V. Increased expression of osteonectin and osteopontin,two bone matrix proteins,in human breast cancer[J]. Am J Pathol, 1995, 146(1): 95-9.
[3]	Nalawade YV. Evaluation of breast calcifications[J]. Ind J Radiol Imag, 2009, 19(4): 282-7.
[4]	Scimeca M, Giannini E, Antonacci C, et al. Microcalcifications in breast cancer: an active phenomenon mediated by epithelial cells with mesenchymal characteristics[J]. BMC Cancer, 2014, 14(1): 1-10.
[5]	Haka AS, Shafer-Peltier KE, Fitzmaurice M, et al. Identifying microcalcifications in benign and malignant breast lesions by probing differences in their chemical composition using Raman spectroscopy[J]. Cancer Res, 2002, 62(18): 5375-81.
[6]	Radi MJ. Calcium oxalate crystals in breast biopsies.An overlooked form of microcalcification associated with benign breast disease[J]. Arch Pathol Lab Med, 1989, 113(12): 1367-9.
[7]	Baker R, Rogers KD, Shepherd N, et al. New relationships between breast microcalcifications and cancer[J]. Br J Cancer, 2010, 103(7): 1034-9.
[8]	Liang LJ, Zheng C, Zhang HP, et al. Exploring type II microcalcifications in benign and premalignant breast lesions by shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS)[J]. Spectrochim Acta A Mol Biomol Spectrosc, 2014, 132(21): 397-402.
[9]	Morgan MP, Cooke MM, Christopherson PA, et al. Calcium hydroxyapatite promotes mitogenesis and matrix metalloproteinase expression in human breast cancer cell lines[J]. Mol Carcinog, 2001, 32(3): 111-7.
[10]	Cox R. Cellular and molecular basis of mammary microcalcifications[M]. Research Gate, 2011.
[11]	Thouverey C, Strzelecka-Kiliszek A, Balcerzak M, et al. Matrix vesicles originate from apical membrane microvilli of mineralizing Osteoblast-Like saos-2 cells[J]. J Cell Biochem, 2009, 106(1): 127-38.
[12]	Galindo-Hernandez O, Gonzales-Vazquez CA, Reyes-Uribe E, et al. Extracellular vesicles from women with breast cancer promote an epithelial-mesenchymal transition-like process in mammary epithelial cells MCF10A[J]. Tumor Biology, 2015, 36(12): 9649-59.
[13]	Kirsch T, Harrison G, Golub EE, et al. The roles of annexins and types II and X collagen in matrix vesicle-mediated mineralization of growth plate cartilage[J]. J Biol Chem, 2000, 275(45): 35577-83.
[14]	Nielsen LB, Pedersen FS, Pedersen L. Expression of type III sodium-dependent phosphate transporters/retroviral receptors mRNAs during osteoblast differentiation[J]. Bone, 2001, 28(2): 160-6.
[15]	Wang T, Gilkes DM, Takano N, et al. Hypoxia-inducible factors and RAB22A mediate formation of microvesicles that stimulate breast cancer invasion and metastasis[J]. Proc Natl Acad Sci USA, 2014, 111(31): E3234-42.
[16]	Kelly-Arnold A, Maldonado N, Laudier DA, et al. Revised microcalcification hypothesis for fibrous cap rupture in human coronary arteries[J]. Proc Natl Acad Sci USA, 2013, 110(26): 10741-6.
[17]	New SE, Goettsch C, Aikawa MA, et al. Macrophage-Derived matrix vesicles: an alternative novel mechanism for microcalcification in atherosclerotic plaques[J]. Circ Res, 2013, 113(1): 72-7.
[18]	Biezynski B, Smith A. Chemical composition of apatites formed by matrix vesicles during bone mineralization[J]. Bioscientifica, 2014, 23(8): 125-32.
[19]	Sarvari B, Mahadev DS, Rupa S, et al. Detection of bone metastases in breast cancer (BC) patients by serum tartrateresistant acid phosphatase 5b (TRACP 5b), a bone resorption marker and serum alkaline phosphatase (ALP), a bone formation marker,in lieu of whole body skeletal scintigraphy with Technetium99m MDP[J]. Indian J Clin Biochem, 2015, 30(1): 66-71.
[20]	Cox RF, Hernandez-Santana A, Ramdass S, et al. Microcalcifications in breast cancer: novel insights into the molecular mechanism and functional consequence of mammary mineralisation[J]. Br J Cancer, 2012, 106(3): 525-37.
[21]	Chen DR, Chien SY, Kuo SJ, et al. SLC34A2 as a novel marker for diagnosis and targeted therapy of breast cancer[J]. Anticancer Res, 2010, 30(10): 4135-40.
[22]	Satokata I, Ma L, Ohshima H, et al. Msx2 deficiency in mice causes pleiotropic defects in bone growth and ectodermal organ formation[J]. Nat Genet, 2000, 24(4): 391-5.
[23]	Montezano AC, Zimmerman D, Yusuf H, et al. Vascular smooth muscle cell differentiation to an osteogenic phenotype involves TRPM7 modulation by Magnesium[J]. Hypertension, 2010, 56(3): 453-U243.
[24]	Sando N, Oka K, Moriya T, et al. Osteosarcoma arising in the breast[J]. APMIS, 2006, 114(7/8): 581-7.
[25]	Lee JS, Lee JM, Im GI. Electroporation-mediated transfer of Runx2 and Osterix genes to enhance osteogenesis of adipose stem cells[J]. Biomaterials, 2011, 32(3): 760-8.
[26]	Lanigan F, Gremel G, Hughes R, et al. Homeobox transcription factor muscle segment homeobox 2 (Msx2) correlates with good prognosis in breast cancer patients and induces apoptosis in vitro[J]. Breast Cancer Res, 2010, 12(4): R59-66.
[27]	Guerreiro S, Monteiro R, Martins MJ, et al. Distinct modulation of alkaline phosphatase isoenzymes by 17 beta-estradiol and xanthohumol in breast cancer MCF-7 cells[J]. Clin Biochem, 2007, 40(3/4): 268-73.
[28]	Usoro NI, Omabbe MC, Usoro CA. Calcium, inorganic phosphates, alkaline and acid phosphatase activities in breast cancer patients in Calabar, Nigeria[J]. Afr Health Sci, 2010, 10(1): 9-13.
[29]	Singh AK, Pandey A, Tewari M, et al. Advanced stage of breast cancer hoist alkaline phosphatase activity: risk factor for females in India[J]. Biotech, 2013, 3(6): 517-20.
[30]	Gillespie MT, Thomas RJ, Pu ZY, et al. Calcitonin receptors,bone sialoprotein and osteopontin are expressed in primary breast cancers[J]. Int J Cancer, 1997, 73(6): 812-7.
[31]	Pratap J, Wixted JJ, Gaur T, et al. Runx2 transcriptional activation of Indian Hedgehog and a downstream bone metastatic pathway in breast cancer cells[J]. Cancer Res, 2008, 68(19): 7795-802.
[32]	Zanette DL, Rivadavia F, Molfetta GA, et al. miRNA expression profiles in chronic lymphocytic and acute lymphocytic leukemia[J]. Brazilian J Med Biol Res, 2007, 40(11): 1435-40.
[33]	Hassan MQ, Maeda Y, Taipaleenmaki H, et al. miR-218 directs a Wnt signaling circuit to promote differentiation of osteoblasts and osteomimicry of metastatic cancer cells[J]. J Biol Chem, 2012, 287(50): 42084-92.
[34]	Kennichi S, Shin H, Kenji K, et al. Up-regulation of MSX2 enhances the malignant phenotype and is associated with twist 1 expression in human pancreatic cancer cells[J]. Am J Pathol, 2008, 172(4): 926-33.
[35]	Wang RN, Green J, Wang Z, et al. Bone morphogenetic protein (BMP) signaling in development and human diseases[J]. Genes Dis, 2014, 1(1): 87-105.
[36]	Liu F, Bloch N, Bhushan KR, et al. Humoral BMP-2 is sufficient for inducing breast cancer microcalcification[J]. Mol Imag, 2008, 7(4): 175-83.
[37]	Li XY, Lu WJ, Fu X, et al. BMP4 increases canonical transient receptor potential protein expression by activating p38 MAPK and ERK1/2 signaling pathways in pulmonary arterial smooth muscle cells[J]. Am J Respir Cell Mol Biol, 2013, 49(2): 212-20.
[38]	Bragdon B, Moseychuk O, Saldanha S, et al. Bone morphogenetic proteins: a critical review[J]. Cell Signal, 2011, 23(4): 609-20.
[39]	Choi ME, Ding Y, Il Kim S. TGF-beta Signaling via TAK1 Pathway: Role in Kidney Fibrosis[J]. Semin Nephrol, 2012, 32(3): 244-52.
[40]	Ghosh-Choudhury N, Woodruff K, Qi WB, et al. Bone morphogenetic protein-2 blocks MDA MB 231 human breast cancer cell proliferation by inhibiting cyclin-dependent kinase-mediated retinoblastoma protein phosphorylation[J]. Biochem Biophys Res Commun, 2000, 272(3): 705-11.
[41]	Choi YJ, Kim ST, Park KH, et al. The serum bone morphogenetic protein-2 level in non-small-cell lung cancer patients[J]. Med Oncol, 2012, 29(2): 582-8.
[42]	Mandal CC, Ghosh-Choudhury T, Dey N, et al. miR-21 is targeted by omega-3 polyunsaturated fatty acid to regulate breast tumor CSF-1 expression[J]. Carcinogenesis, 2012, 33(10): 1897-908.
[43]	Kacinski BM. CSF‐1 and its receptor in breast carcinomas and neoplasms of the female reproductive tract[J]. Molecul Reprod Developm, 1997, 46(1): 71-4.
[44]	Shih JY, Yuan A, Chen JW, et al. Tumor-Associated macrophage:its role in cancer invasion and metastasis[J]. J Cancer Molecules, 2006, 2(3): 101-6.
[45]	Yam M, Tchou J, English R, et al. A mammographic dilemma:calcification or haemosiderin as a cause of opacities? Validation of a new digital diagnostic tool[J]. British J Radiol, 2001, 74(887): 1048-51.