Decreased metastatic phenotype in cells resistant to aminolevulinic acid-photodynamic therapy.
Photodynamic therapy (PDT) is a novel cancer treatment utilising a photosensitiser, visible light and oxygen. PDT often leaves a significant number of surviving tumour cells. In a previous work, we isolated and studied two PDT resistant clones derived from the mammary adenocarcinoma LM3 line (Int. J. Oncol. 29 (2006) 397-405). The isolated Clon 4 and Clon 8 exhibited a more fibroblastic, dendritic pattern and were larger than the parentals. In the present work we studied the metastatic potential of the two clones in comparison with LM3. We found that 100% of LM3 invaded Matrigel, whereas only 19+/-6% and 24+/-7% of Clon 4 and Clon 8 cells invaded. In addition, 100% of LM3 cells migrated towards a chemotactic stimulus whereas 38+/-8% and 73+/-10% of Clones 4 and 8, respectively, were able to migrate. In vivo, 100% of the LM3 injected mice developed spontaneous lung metastasis, whereas none of the Clon 8 did, and only one of the mice injected with Clon 4 did. No differences were found in the proteolytic enzyme profiles among the cells. Anchorage-dependent adhesion was also impaired in vivo in the resistant clones, evidenced by the lower tumour take, latency time and growth rates, although both clones showed in vitro higher binding to collagen I without overexpression of beta1 integrin. This is the first work where the metastatic potential of cells surviving to PDT has been studied. PDT strongly affects the invasive phenotype of these cells, probably related to a higher binding to collagen. These findings may be crucial for the outcome of ALA-PDT of metastatic tumours, although further studies are needed to extrapolate the results to the clinic employing another photosensitisers and cell types.
Casas
Adriana
A
Centro de Investigaciones sobre Porfirinas y Porfirias, CONICET and Hospital de Clínicas José de San Martín, University of Buenos Aires, 1056 Ciudad de Buenos Aires, Córdoba 2351 1er subsuelo, CP 1120AAF, Buenos Aires, Argentina. adriana@qb.fcen.uba.ar
Di Venosa
Gabriela
G
Vanzulli
Silvia
S
Perotti
Christian
C
Mamome
Leandro
L
Rodriguez
Lorena
L
Simian
Marina
M
Juarranz
Angeles
A
Pontiggia
Osvaldo
O
Hasan
Tayyaba
T
Batlle
Alcira
A
D000622:Aminolevulinic Acid / Q000627:therapeutic use*; D000818:Animals; D002448:Cell Adhesion; D019008:Drug Resistance, Neoplasm; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D010778:Photochemotherapy
D000622:Aminolevulinic Acid