The molecular mechanisms underlying the ‘seed and soil’ theory are unknown. S100A8/A9 (a heterodimer complex of S100A8 and S100A9 proteins that exhibits a ‘soil signal’) is a ligand for Toll-like receptor 4, causing distant melanoma cells to approach the lung as a ‘seeding’ site. Unknown soil sensors for S100A8/A9 may exist, e.g., extracellular matrix metalloproteinase inducer, neuroplastin, activated leukocyte cell adhesion molecule, and melanoma cell adhesion molecule. We call these receptor proteins ‘novel S100 soil sensor receptors (novel SSSRs).’ Here we review and summarize a crucial role of the S100A8/A9-novel SSSRs' axis in cancer metastasis. The binding of S100A8/A9 to individual SSSRs is important in cancer metastasis via upregulations of the epithelial-mesenchymal transition, cellular motility, and cancer cell invasiveness, plus the formation of an inflammatory immune suppressive environment in metastatic organ(s). These metastatic cellular events are caused by the SSSR-featured signal transductions we identified that provide cancer cells a driving force for metastasis. To deprive cancer cells of these metastatic forces, we developed novel biologics that prevent the interaction of S100A8/A9 with SSSRs, followed by the efficient suppression of S100A8/A9-mediated lung-tropic metastasis in vivo.

“种子和土壤”理论的分子机制尚不清楚。S100A8 / A9（S100A8和S100A9蛋白的异二聚体复合物表现出“土壤信号”）是Toll样受体4的配体，导致远处的黑色素瘤细胞进入肺部成为“播种”位点。可能存在未知的S100A8 / A9土壤传感器，例如，细胞外基质金属蛋白酶诱导剂，神经增塑剂，活化的白细胞粘附分子和黑素瘤细胞粘附分子。我们称这些受体蛋白为“新型S100土壤传感器受体（新型SSSR）”。在这里，我们回顾并总结了S100A8 / A9-novel SSSRs轴在癌症转移中的关键作用。S100A8 / A9与单个SSSR的结合通过上皮-间质转化，细胞运动性和癌细胞侵袭性的上调在癌症转移中很重要，在转移器官中形成炎性免疫抑制环境。这些转移性细胞事件是由我们确定的SSSR功能信号转导所引起的，这些信号转导为癌细胞提供了转移的驱动力。为了剥夺癌细胞的这些转移力，我们开发了新颖的生物制剂，可防止S100A8 / A9与SSSR相互作用，随后有效抑制S100A8 / A9介导的体内肺转移。