Cancer metastasis can occur at the early stage of tumor development when a primary tumor is at the microscopic size. In particular, the interaction of malignant cells with other cell types including cancer-associated fibroblasts (CAF) in promoting metastasis at the early stage of tumor development remains largely unknown. Here, we investigated the role of CAFs in facilitating the initial events of cancer metastasis when primary tumors were at microscopic sizes. Multicolor-coded cancer cells and CAFs were coimplanted into the transparent zebrafish body and metastasis at a single-cell level was monitored in living animals. Healthy fibroblasts, tumor factor-educated fibroblasts, and CAFs isolated from various tumors were tested for their ability to facilitate metastasis. We showed that CAFs promoted cancer cell metastasis at the very early stage during primary tumor development. When a primary tumor was at the microscopic size consisting of a few hundred cells, CAFs were able to hijack cancer cells for dissemination from the primary site. Surprisingly, a majority of metastatic cancer cells remained in tight association with CAFs in the circulation. Furthermore, stimulation of non-metastasis-promoting normal fibroblasts with TGF-B, FGF-2, HGF, and PDGF-BB led to acquisition of their metastatic capacity. Cancer metastasis occurs at the very early stage of tumor formation consisting of only a few hundred cells. CAFs are the key cellular determinant for metastasis. Our findings provide novel mechanistic insights on CAFs in promoting cancer metastasis and targeting CAFs for cancer therapy should be aimed at the early stage during cancer development. .

Although several cases of family clusters with SARS-Cov-2 infection have been reported, there are still limited data preventing conclusions from being drawn regarding the characteristics and laboratory findings in the COVID-19 population within family clusters. In the present study, we retrospectively collected five family clusters with COVID-19 and summarized the dynamic profiles of the clinical characteristics, laboratory findings, immune markers, treatment and prognosis of this population. Furthermore, we also compared clinical and laboratory data between the SARS-Cov-2 infection with family cluster (n = 21) and those without family cluster (n = 16). We demonstrated that the duration of SARS-Cov-2 replication might be varied based on the different family clusters due to their different genetic backgrounds. The onset improved lung radiology might start at the end of the SARS-Cov-2 positive period. Furthermore, the obtained results demonstrated that similar basic characteristics and clinical findings seem to exist between the cases with SARS-Cov-2 and without family clusters. The serum level of ferritin might have a different biological function and be a new biomarker for the family cluster. Further studies with larger numbers of patients are required.