title: Macrophages of M1 phenotype have properties that influence lung cancer cell progression.
abstract: Stromal macrophages of different phenotypes can contribute to the expression of proteins that affects metastasis such as urokinase-type plasminogen activator (uPA), its receptor uPAR, and plasminogen activator inhibitor-1 (PAI-1), but knowledge of how essential their contribution is in comparison to the cancer cells in small cell lung cancer (SCLC) and lung squamous cell carcinoma (SCC) is lacking. The expression of uPA, uPAR, and PAI-1 and of the matrix metalloproteinases (MMP)-2 and MMP-9 were studied in human macrophages of M1 and M2 phenotype and compared to a lung SCC (NCI-H520) and a SCLC (NCI-H69) cell line. Effects of treatment with conditioned media (CM) from M1 and M2 macrophages on the expression of these genes in H520 and H69 cells as well as effects on the cell growth were investigated. In addition, data on the stromal macrophages immunoreactivity of uPAR, MMP-2, and MMP-9 in a few SCC and SCLC biopsies was included. uPAR, MMP-2, and MMP-9 were confirmed in stromal cells including macrophages in the SCC and SCLC biopsies. In vitro, both macrophage phenotypes expressed considerably higher mRNA levels of uPA, uPAR, PAI-1, and MMP-9 compared to the cancer cell lines, and regarding uPAR, the highest level was found in the M1 macrophage phenotype. Furthermore, M1 CM treatment not only induced an upregulation of PAI-1 in both H520 and H69 cells but also inhibited cell growth in both cell lines, giving M1 macrophages both tumor-promoting and tumor-killing potential.
authors.affiliation: Department of Health Sciences, Karlstad University, 651 88, Karlstad, Sweden.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hedbrant
authors.affiliation: Department of Health Sciences, Karlstad University, 651 88, Karlstad, Sweden.
authors.forename: Jonny
authors.initials: J
authors.lastname: Wijkander
authors.affiliation: Department of Health Sciences, Karlstad University, 651 88, Karlstad, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Seidal
authors.affiliation: School of Health and Medical Science, Örebro University, 702 81, Örebro, Sweden.
authors.forename: Dick
authors.initials: D
authors.lastname: Delbro
authors.affiliation: Department of Health Sciences, Karlstad University, 651 88, Karlstad, Sweden. ann.erlandsson@kau.se.
authors.forename: Ann
authors.initials: A
authors.lastname: Erlandsson
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D055293:Receptors, Urokinase Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics; D055752:Small Cell Lung Carcinoma / Q000235:genetics* / Q000473:pathology; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D055293:Receptors, Urokinase Plasminogen Activator; C051321:SERPINE1 protein, human; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Lung cancer; M1 macrophages; M2 macrophages; MMP; uPA; uPAR