Hepatocyte growth factor (HGF) is a multifunctional cytokine with effects on the proliferation, motility, and differentiation of cells that express its receptor Met. The co-expression of HGF and Met is common among nonsmall-cell lung cancers, especially adenocarcinoma. However, the biologic consequences of this putative HGF-Met autocrine signaling remain speculative. We have used retroviral gene transduction technique to express high levels of HGF in the NCI-H358 lung adenocarcinoma cells that have functionally active cell surface Met receptor. The activation of autocrine HGF-Met signaling was confirmed by the induction of spontaneous cell scattering activity. Compared to the parent and control cells transduced with the retroviral vector alone, HGF overexpressing H358 cells show enhanced capacity to colonize soft agar medium and to form xenograft tumors when implanted in the subcutaneous tissue of immune-deficient mice. These effects were not accompanied by changes in their growth rate in monolayer culture condition, or in the expression of vascular endothelial growth factor. The tumors formed by HGF overexpressing cells also showed more prominent glandular cell arrangement and functional activity. This report provides the direct in vivo evidence that autocrine HGF-Met signaling plays significant roles in the growth and differentiation of human lung adenocarcinoma cells.

Background: Nonpharmaceutical interventions (NPIs) are the primary tools to mitigate early spread of the coronavirus disease 2019 (COVID-19) pandemic; however, such policies are implemented variably at the federal, provincial or territorial, and municipal levels without centralized documentation. We describe the development of the comprehensive open Canadian Non-Pharmaceutical Intervention (CAN-NPI) data set, which identifies and classifies all NPIs implemented in regions across Canada in response to COVID-19, and provides an accompanying description of geographic and temporal heterogeneity. Methods: We performed an environmental scan of government websites, news media and verified government social media accounts to identify NPIs implemented in Canada between Jan. 1 and Apr. 19, 2020. The CAN-NPI data set contains information about each intervention's timing, location, type, target population and alignment with a response stringency measure. We conducted descriptive analyses to characterize the temporal and geographic variation in early NPI implementation. Results: We recorded 2517 NPIs grouped in 63 distinct categories during this period. The median date of NPI implementation in Canada was Mar. 24, 2020. Most jurisdictions heightened the stringency of their response following the World Health Organization's global pandemic declaration on Mar. 11, 2020. However, there was variation among provinces or territories in the timing and stringency of NPI implementation, with 8 out of 13 provinces or territories declaring a state of emergency by Mar. 18, and all by Mar. 22, 2020. Interpretation: There was substantial geographic and temporal heterogeneity in NPI implementation across Canada, highlighting the importance of a subnational lens in evaluating the COVID-19 pandemic response. Our comprehensive open-access data set will enable researchers to conduct robust interjurisdictional analyses of NPI impact in curtailing COVID-19 transmission.