Adult human mesenchymal stem cells enhance breast tumorigenesis and promote hormone independence.
Adult human mesenchymal stem cells (hMSCs) have been shown to home to sites of breast cancer and integrate into the tumor stroma. We demonstrate here the effect of hMSCs on primary breast tumor growth and the progression of these tumors to hormone independence. Co-injection of bone marrow-derived hMSCs enhances primary tumor growth of the estrogen receptor-positive, hormone-dependent breast carcinoma cell line MCF-7 in the presence or absence of estrogen in SCID/beige mice. We also show hormone-independent growth of MCF-7 cells when co-injected with hMSCs. These effects were found in conjunction with increased immunohistochemical staining of the progesterone receptor in the MCF-7/hMSC tumors as compared to MCF-7 control tumors. This increase in PgR expression indicates a link between MCF-7 cells and MSCs through ER-mediated signaling. Taken together, our data reveal the relationship between tumor microenvironment and tumor growth and the progression to hormone independence. This tumor stroma-cell interaction may provide a novel target for the treatment of estrogen receptor-positive, hormone-independent, and endocrine-resistant breast carcinoma.
Rhodes
Lyndsay V
LV
Department of Medicine, Section of Hematology & Medical Oncology, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
Muir
Shannon E
SE
Elliott
Steven
S
Guillot
Lori M
LM
Antoon
James W
JW
Penfornis
Patrice
P
Tilghman
Syreeta L
SL
Salvo
Virgilio A
VA
Fonseca
Juan P
JP
Lacey
Michelle R
MR
Beckman
Barbara S
BS
McLachlan
John A
JA
Rowan
Brian G
BG
Pochampally
Radhika
R
Burow
Matthew E
ME
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D045744:Cell Line, Tumor; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone