Surfactant protein a suppresses lung cancer progression by regulating the polarization of tumor-associated macrophages

Atsushi Mitsuhashi, Hisatsugu Goto, Takuya Kuramoto, Sho Tabata, Sawaka Yukishige, Shinji Abe, Masaki Hanibuchi, Soji Kakiuchi, Atsuro Saijo, Yoshinori Aono, Hisanori Uehara, Seiji Yano, Julie G. Ledford, Saburo Sone, Yasuhiko Nishioka

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Surfactant protein A (SP-A) is a large multimeric protein found in the lungs. In addition to its immunoregulatory function in infectious respiratory diseases, SP-A is also used as a marker of lung adenocarcinoma. Despite the finding that SP-A expression levels in cancer cells has a relationship with patient prognosis, the function of SP-A in lung cancer progression is unknown. We investigated the role of SP-A in lung cancer progression by introducing the SP-A gene into human lung adenocarcinoma cell lines. SP-A gene transduction suppressed the progression of tumor in subcutaneous xenograft or lung metastasis mouse models. Immunohistochemical analysis showed that the number of M1 antitumor tumor-associated macrophages (TAMs) was increased and the number of M2 tumor-promoting TAMs was not changed in the tumor tissue produced by SP-A-expressing cells. In addition, natural killer (NK) cells were also increased and activated in the SP-A-expressing tumor. Moreover, SP-A did not inhibit tumor progression in mice depleted of NK cells. Taking into account that SP-A did not directly activate NK cells, these results suggest that SP-A inhibited lung cancer progression by recruiting and activating NK cells via controlling the polarization of TAMs.

Original languageEnglish (US)
Pages (from-to)1843-1853
Number of pages11
JournalAmerican Journal of Pathology
Volume182
Issue number5
DOIs
StatePublished - May 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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