American Association for Cancer Research
00085472can133339-sup-122960_3_supp_0_ng4bx9.pdf (11.22 MB)

Supplementary Figures 1-5 from Role of Chitinase 3–like-1 and Semaphorin 7a in Pulmonary Melanoma Metastasis

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journal contribution
posted on 2023-03-30, 22:30 authored by Bing Ma, Erica L. Herzog, Chun Geun Lee, Xueyan Peng, Chang-Min Lee, Xiaosong Chen, Sara Rockwell, Ja Seok Koo, Harriet Kluger, Roy S. Herbst, Mario Sznol, Jack A. Elias

Supplementary Figures 1-5. Supplementary Figure 1. Dose and time kinetic evaluation of the production of Chi3l1 by recombinant murine Sema7a (rmSema7a) stimulated macrophages. Supplementary Figure 2. Double label immunohistochemical staining of CD4, Ly-6G, and Chi3l1. Supplementary Figure 3. Growth of melanoma cells 10 weeks of B16-F10 cell subcutaneous (s.c.) inoculation. Supplementary Figure 4. The expression of Chi3l1 and Sema7a in lungs with and without metastatic breast cancer cells. Supplementary Figure 5. Role of integrin β3 in Sema7a-stimualted expression of Chi3l1.



The prototypic chitinase-like protein Chi3l1 is induced in cancers and portends a poor prognosis, but whether it contributes to cancer progression is unknown. To address this gap in knowledge, we investigated the production of Chi3l1 in melanoma lung metastases. We found that Chi3l1 was induced during pulmonary melanoma metastasis and that this induction was regulated by the semaphorin Sema7a, interacting in stimulatory or inhibitory ways with its β1 integrin or Plexin C1 receptors, respectively. In mouse strains with genetic deletions of Chi3l1 or Sema7a, there was a significant reduction in pulmonary metastasis. Notably, antiserum raised against Chi3l1 or Sema7a phenocopied the reduction produced by genetic deletions. Melanoma lung metastasis was also decreased in the absence of IL13Rα2, a recently identified receptor for Chi3l1, consistent with a key role for Chi3l1 in melanoma spread. We confirmed roles for Sema7a and Chi3l1 in pulmonary metastasis of EMT6 breast cancer cells. Taken together, our studies establish a novel pathway through which Sem7a and its receptors regulate Chi3l1, revealing a host axis involving IL13Rα2 that plays a critical role in generating a pulmonary microenvironment that is critical to license metastasis. Cancer Res; 75(3); 487–96. ©2014 AACR.

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