Tumor-associated macrophages (TAMs) are the most abundant inflammatory infiltrates in the tumor microenvironment and contribute to lymph node (LN) metastasis. However, the precise mechanisms of TAMs-induced LN metastasis remain largely unknown. Herein, we identify a long noncoding RNA, termed Lymph Node Metastasis Associated Transcript 1 (LNMAT1), which is upregulated in LN-positive bladder cancer and associated with LN metastasis and prognosis. Through gain and loss of function approaches, we find that LNMAT1 promotes bladder cancer-associated lymphangiogenesis and lymphatic metastasis. Mechanistically, LNMAT1 epigenetically activates CCL2 expression by recruiting hnRNPL to CCL2 promoter, which leads to increased H3K4 tri-methylation that ensures hnRNPL binding and enhances transcription. Furthermore, LNMAT1-induced upregulation of CCL2 recruits macrophages into the tumor, which promotes lymphatic metastasis via VEGF-C excretion. These findings provide a plausible mechanism for LNMAT1-modulated tumor microenvironment in lymphatic metastasis and suggest that LNMAT1 may represent a potential therapeutic target for clinical intervention in LN-metastatic bladder cancer.

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Wet filter paper is central to a powerful new method of mass spectrometry presented by G. Cooks, Z. Ouyang et al. in their Communication on p. 877 ff. Samples can be preloaded onto the paper, added from solution, or transferred from surfaces using the paper as a wipe. Potential applications lie in quantitative analysis of whole blood from finger pricks or in surface wipe-and-analyze experiments for security applications, and in in situ analysis.

Paper spray mass spectrometry (PS-MS) is explored as a fast and convenient way for direct analysis of molecules in tissues with minimum sample pretreatment. This technique allows direct detection of different types of molecules such as hormones, lipids and therapeutic drugs in short total analysis times (less than one minute) using a small volume of tissue sample (typically 1 mm 3 or less). The tissue sample could be obtained by needle aspiration biopsy, by punch biopsy, or by rubbing a thin tissue section across the paper. There exists potential for the application of paper spray mass spectrometry together with tissue biopsy for clinical diagnostics.

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