Immunohematology Laboratory, Experimental Biology and Medicine Institute (IBYME), National Council of Scientific and Technical Research (CONICET), 2490 Vuelta de Obligado, 1428, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
Clin Exp Metastasis. 2014 Feb;31(2):213-32. doi: 10.1007/s10585-013-9622-5. Epub 2013 Oct 31.
Bone metastasis is an incurable complication of breast cancer affecting 70-80 % of advanced patients. It is a multistep process that includes tumour cell mobilisation, intravasation, survival in the circulation, extravasation, migration and proliferation in the bone marrow/bone. Although novel findings demonstrate the bone marrow microenvironment significance in bone metastatic progression, a majority of studies have focused on end-stage disease and little is known about how the pre-metastatic niche arises in the bone marrow/bone tissues. We demonstrated a significant increase in patients' peripheral blood plasma ability to induce transendothelial migration of MCF-7 cells compared with healthy volunteers. Moreover, high RANKL, MIF and OPG levels in patients' peripheral blood could play a role in the intravasation, angiogenesis, survival and epithelial-mesenchymal transition of circulating tumour cells. Also, we observed a significant increase in patients' bone marrow plasma capacity to induce transendothelial migration of MDA-MB231 and MCF-7 cells compared with healthy volunteers. Furthermore, patients' bone marrow mesenchymal stem cells could control the recruitment of tumour cells, modifying the MCF-7 and MDA-MB231 cell migration. In addition, we found a significantly higher MDA-MB231 cell proliferation when we used patients' bone marrow plasma compared with healthy volunteers. Interestingly, PDGF-AB, ICAM-1 and VCAM-1 levels in patients' bone marrow were significantly higher than the values of healthy volunteers, suggesting that they could be involved in the cancer cell extravasation, bone resorption and cancer cell proliferation. We believe that these results can reveal new information about what alterations happen in the bone marrow of advanced breast cancer patients before bone colonisation, changes that create optimal soil for the metastatic cascade progression.
骨转移是一种不可治愈的乳腺癌并发症，影响 70-80%的晚期患者。它是一个多步骤的过程，包括肿瘤细胞的动员、血管内渗、在循环中的存活、外渗、在骨髓/骨中的迁移和增殖。尽管新的发现表明骨髓微环境在骨转移进展中的重要性，但大多数研究都集中在晚期疾病上，对于转移前龛在骨髓/骨组织中是如何产生的知之甚少。我们发现患者外周血血浆诱导 MCF-7 细胞跨内皮迁移的能力与健康志愿者相比显著增加。此外，患者外周血中高 RANKL、MIF 和 OPG 水平可能在循环肿瘤细胞的血管内渗、血管生成、存活和上皮-间充质转化中发挥作用。此外，我们观察到患者骨髓血浆诱导 MDA-MB231 和 MCF-7 细胞跨内皮迁移的能力与健康志愿者相比显著增加。此外，患者骨髓间充质干细胞可以控制肿瘤细胞的募集，改变 MCF-7 和 MDA-MB231 细胞的迁移。此外，当我们使用患者骨髓血浆时，我们发现 MDA-MB231 细胞的增殖显著增加，而健康志愿者则没有。有趣的是，患者骨髓中的 PDGF-AB、ICAM-1 和 VCAM-1 水平明显高于健康志愿者，表明它们可能参与癌细胞外渗、骨吸收和癌细胞增殖。我们认为这些结果可以揭示关于晚期乳腺癌患者在骨髓定植之前发生了哪些变化的新信息，这些变化为转移级联进展创造了最佳的土壤。
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