Lymphatic metastasis of breast cancer cells is associated with differential gene expression profiles that predict cancer stem cell-like properties and the ability to survive, establish and grow in a foreign environment.
Although lymphatic dissemination is a major route for breast cancer metastasis, there has been little work to determine what factors control the ability of tumor cells to survive, establish and show progressive growth in a lymph node environment. This information is of particular relevance now, in the era of sentinel lymph node biopsy, where smaller intranodal tumor deposits are being detected earlier in the course of disease, the clinical relevance of which is uncertain. In this study, we compared differentially expressed genes in cell lines of high (468LN) vs. low (468GFP) lymphatic metastatic ability, and related these to clinical literature on genes associated with lymphatic metastatic ability and prognosis, to identify genes of potential clinical relevance. This approach revealed differential expression of a set of genes associated with 'cancer stem cell-like' properties, as well as networks of genes potentially associated with survival and autonomous growth. We explored these differences functionally and found that 468LN cells have a higher proportion of cells with a cancer stem cell-like (CD44+/CD24-) phenotype, have a higher clonogenic potential and a greater ability to survive, establish and grow in a foreign (lymph node and 3D Matrigel) microenvironment, relative to 468GFP cells. Differentially expressed genes which reflect these functions provide candidates for investigation as potential targets for therapy directed against early lymphatic metastasis.
Pandit
Terlika S
TS
London Regional Cancer Program, London Health Sciences Centre, London, Ontario, Canada.
Kennette
Wendy
W
Mackenzie
Lisa
L
Zhang
Guihua
G
Al-Katib
Waleed
W
Andrews
Joseph
J
Vantyghem
Sharon A
SA
Ormond
D George
DG
Allan
Alison L
AL
Rodenhiser
David I
DI
Chambers
Ann F
AF
Tuck
Alan B
AB
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D051927:CD24 Antigen / Q000032:analysis; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D008207:Lymphatic Metastasis; D051379:Mice; D014411:Neoplastic Stem Cells / Q000473:pathology*
D051927:CD24 Antigen; C497889:CD24 protein, human; C497483:CD44 protein, human; D018960:Hyaluronan Receptors