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Mesenchymal Stem Cells Shed Amphiregulin at the Surface of Lung Carcinoma Cells in a Juxtacrine Manner.

Carnet O, Lecomte J, Masset A, Primac I, Durré T, Maertens L, Detry B, Blacher S, Gilles C, Péqueux C, Paupert J, Foidart JM, Jerusalem G, Cataldo D, Noel A - Neoplasia (2015)

Bottom Line: The proinvasive effect of BM-MSCs exerted on tumor cells relies on an unprecedented juxtacrine action of BM-MSC, leading to the trans-shedding of amphiregulin (AREG) from the tumor cell membrane by tumor necrosis factor-α-converting enzyme carried by the BM-MSC plasma membrane.This novel concept is supported by the exploitation of different 2D and 3D culture systems and by pharmacological approaches using a tumor necrosis factor-α-converting enzyme inhibitor and AREG-blocking antibodies.Altogether, we here assign a new function to BM-MSC in tumor progression and establish an uncovered link between AREG and BM-MSC.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liège, B-4000 Liège, Belgium.

No MeSH data available.


Related in: MedlinePlus

BM-MSCs promote LLC cell proliferation and invasion.LLC cells were cultured alone (LLC, monoculture) or co-cultured with MSCs (LLC+MSC) in direct contact (direct co-culture) or separated by a semipermeable membrane in a transwell chamber (LLC/MSC, indirect co-culture). Cells were either seeded on plastic (A, B) or embedded as spheroids in a collagen gel (C). (B) Quantitative analysis of the luminescence intensity of Luc-LLC cells cultured for 3 days with or without BM-MSCs (Mann-Whitney: **P < .01; ***P < .001). (C) The invasion of LLC cells in the 3D spheroid model is increased in the presence of BM-MSCs (LLC+MSC) (Mann-Whitney: ***P < .001). In the lower panel, the spheroid is composed of LLC cells and GFP+ BM-MSCs, revealing that only cancer cells migrate into the matrix, whereas BM-MSCs remain in the spheroid (green cells). The graph corresponds to the quantification of cell invasion.
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f0015: BM-MSCs promote LLC cell proliferation and invasion.LLC cells were cultured alone (LLC, monoculture) or co-cultured with MSCs (LLC+MSC) in direct contact (direct co-culture) or separated by a semipermeable membrane in a transwell chamber (LLC/MSC, indirect co-culture). Cells were either seeded on plastic (A, B) or embedded as spheroids in a collagen gel (C). (B) Quantitative analysis of the luminescence intensity of Luc-LLC cells cultured for 3 days with or without BM-MSCs (Mann-Whitney: **P < .01; ***P < .001). (C) The invasion of LLC cells in the 3D spheroid model is increased in the presence of BM-MSCs (LLC+MSC) (Mann-Whitney: ***P < .001). In the lower panel, the spheroid is composed of LLC cells and GFP+ BM-MSCs, revealing that only cancer cells migrate into the matrix, whereas BM-MSCs remain in the spheroid (green cells). The graph corresponds to the quantification of cell invasion.

Mentions: Taking advantage of the luciferase expression by LLC cells, the proliferation of LLC cells was evaluated by bioluminescence detection after luciferin administration. Three conditions were tested: 1) LLC cells alone, 2) LLC directly co-cultured with BM-MSCs, and 3) co-culture of LLC cells separated from BM-MSCs by a semipermeable membrane to avoid direct cell–cell contacts (Figure 3A). In direct 2D co-cultures, the LLC cell number was significantly increased after 72 hours of culture, whereas tumor cell proliferation was not affected in indirect co-culture conditions (Figure 3B). In a 3D spheroid invasion assay, LLC cell invasive properties were stimulated when tumor cells were mixed with BM-MSCs compared with the invasion of LLC cells as monospheroids (Figure 3C). The use of GFP-expressing BM-MSCs in this assay demonstrated that the migrating cells were LLC cells rather than BM-MSCs (Figure 3C). Indeed, GFP-positive cells remained inside the spheroid, whereas LLC cells were able to spread out and invade the surrounding type I collagen matrix.


Mesenchymal Stem Cells Shed Amphiregulin at the Surface of Lung Carcinoma Cells in a Juxtacrine Manner.

Carnet O, Lecomte J, Masset A, Primac I, Durré T, Maertens L, Detry B, Blacher S, Gilles C, Péqueux C, Paupert J, Foidart JM, Jerusalem G, Cataldo D, Noel A - Neoplasia (2015)

BM-MSCs promote LLC cell proliferation and invasion.LLC cells were cultured alone (LLC, monoculture) or co-cultured with MSCs (LLC+MSC) in direct contact (direct co-culture) or separated by a semipermeable membrane in a transwell chamber (LLC/MSC, indirect co-culture). Cells were either seeded on plastic (A, B) or embedded as spheroids in a collagen gel (C). (B) Quantitative analysis of the luminescence intensity of Luc-LLC cells cultured for 3 days with or without BM-MSCs (Mann-Whitney: **P < .01; ***P < .001). (C) The invasion of LLC cells in the 3D spheroid model is increased in the presence of BM-MSCs (LLC+MSC) (Mann-Whitney: ***P < .001). In the lower panel, the spheroid is composed of LLC cells and GFP+ BM-MSCs, revealing that only cancer cells migrate into the matrix, whereas BM-MSCs remain in the spheroid (green cells). The graph corresponds to the quantification of cell invasion.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4547406&req=5

f0015: BM-MSCs promote LLC cell proliferation and invasion.LLC cells were cultured alone (LLC, monoculture) or co-cultured with MSCs (LLC+MSC) in direct contact (direct co-culture) or separated by a semipermeable membrane in a transwell chamber (LLC/MSC, indirect co-culture). Cells were either seeded on plastic (A, B) or embedded as spheroids in a collagen gel (C). (B) Quantitative analysis of the luminescence intensity of Luc-LLC cells cultured for 3 days with or without BM-MSCs (Mann-Whitney: **P < .01; ***P < .001). (C) The invasion of LLC cells in the 3D spheroid model is increased in the presence of BM-MSCs (LLC+MSC) (Mann-Whitney: ***P < .001). In the lower panel, the spheroid is composed of LLC cells and GFP+ BM-MSCs, revealing that only cancer cells migrate into the matrix, whereas BM-MSCs remain in the spheroid (green cells). The graph corresponds to the quantification of cell invasion.
Mentions: Taking advantage of the luciferase expression by LLC cells, the proliferation of LLC cells was evaluated by bioluminescence detection after luciferin administration. Three conditions were tested: 1) LLC cells alone, 2) LLC directly co-cultured with BM-MSCs, and 3) co-culture of LLC cells separated from BM-MSCs by a semipermeable membrane to avoid direct cell–cell contacts (Figure 3A). In direct 2D co-cultures, the LLC cell number was significantly increased after 72 hours of culture, whereas tumor cell proliferation was not affected in indirect co-culture conditions (Figure 3B). In a 3D spheroid invasion assay, LLC cell invasive properties were stimulated when tumor cells were mixed with BM-MSCs compared with the invasion of LLC cells as monospheroids (Figure 3C). The use of GFP-expressing BM-MSCs in this assay demonstrated that the migrating cells were LLC cells rather than BM-MSCs (Figure 3C). Indeed, GFP-positive cells remained inside the spheroid, whereas LLC cells were able to spread out and invade the surrounding type I collagen matrix.

Bottom Line: The proinvasive effect of BM-MSCs exerted on tumor cells relies on an unprecedented juxtacrine action of BM-MSC, leading to the trans-shedding of amphiregulin (AREG) from the tumor cell membrane by tumor necrosis factor-α-converting enzyme carried by the BM-MSC plasma membrane.This novel concept is supported by the exploitation of different 2D and 3D culture systems and by pharmacological approaches using a tumor necrosis factor-α-converting enzyme inhibitor and AREG-blocking antibodies.Altogether, we here assign a new function to BM-MSC in tumor progression and establish an uncovered link between AREG and BM-MSC.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liège, B-4000 Liège, Belgium.

No MeSH data available.


Related in: MedlinePlus