Zhang Chi, Winnard Paul T, Dasari Sidarth, Kominsky Scott L, Doucet Michele, Jayaraman Swaathi, Raman Venu, Barman Ishan
Department of Mechanical Engineering , Johns Hopkins University , Whiting School of Engineering , Latrobe Hall 103 , Baltimore , MD 21218 , USA . Email:
Division of Cancer Imaging Research , Russell H. Morgan Department of Radiology and Radiological Science , Johns Hopkins University School of Medicine , 720 Rutland Avenue, Rm 340 Traylor Building , Baltimore , MD , USA 21205 . Email:
Chem Sci. 2017 Nov 15;9(3):743-753. doi: 10.1039/c7sc02905e. eCollection 2018 Jan 21.
Breast neoplasms frequently colonize bone and induce development of osteolytic bone lesions by disrupting the homeostasis of the bone microenvironment. This degenerative process can lead to bone pain and pathological bone fracture, a major cause of cancer morbidity and diminished quality of life, which is exacerbated by our limited ability to monitor early metastatic disease in bone and assess fracture risk. Spurred by its label-free, real-time nature and its exquisite molecular specificity, we employed spontaneous Raman spectroscopy to assess and quantify early metastasis driven biochemical alterations to bone composition. As early as two weeks after intracardiac inoculations of MDA-MB-435 breast cancer cells in NOD-SCID mice, Raman spectroscopic measurements in the femur and spine revealed consistent changes in carbonate substitution, overall mineralization as well as crystallinity increase in tumor-bearing bones when compared with their normal counterparts. Our observations reveal the possibility of early stage detection of biochemical changes in the tumor-bearing bones - significantly before morphological variations are captured through radiographic diagnosis. This study paves the way for a better molecular understanding of altered bone remodeling in such metastatic niches, and for further clinical studies with the goal of establishing a non-invasive tool for early metastasis detection and prediction of pathological fracture risk in breast cancer.
乳腺肿瘤常转移至骨骼，并通过破坏骨微环境的稳态诱导溶骨性骨病变的发展。这种退行性过程可导致骨痛和病理性骨折，这是癌症发病率和生活质量下降的主要原因，而我们监测早期骨转移疾病和评估骨折风险的能力有限，这使得情况更加恶化。受其无标记、实时特性及其精湛的分子特异性的启发，我们采用自发拉曼光谱来评估和量化早期转移驱动的骨成分生化改变。早在将MDA-MB-435乳腺癌细胞经心内接种到NOD-SCID小鼠体内两周后，对股骨和脊柱进行的拉曼光谱测量就显示，与正常对应部位相比，荷瘤骨中的碳酸盐取代、总体矿化以及结晶度增加都有一致的变化。我们的观察结果揭示了在荷瘤骨中早期检测生化变化的可能性——远在通过放射学诊断捕捉到形态学变化之前。这项研究为更好地从分子层面理解此类转移微环境中改变的骨重塑，以及为进一步的临床研究铺平了道路，目标是建立一种用于乳腺癌早期转移检测和病理性骨折风险预测的非侵入性工具。
