Macrophages promote primary tumor growth and metastatic dissemination
through a variety of mechanisms. This thesis examined the ability of RAW 264.7
murine macrophages to elicit malignant behaviors from a series of murine
mammary carcinoma cell lines (4T1, 66cl4, 4TO7, 67NR) that differ extensively in
their metastatic potential when transplanted in vivo. It was hypothesized that the
RAW 264.7 macrophages would evoke malignant behaviors from the carcinoma
cells in vitro, but in a way that correlated with the metastatic nature of each line.
Conditioned media experiments revealed that paracrine cues from the RAW
264.7s induced the expression of Sca-1, a murine surface marker known to
represent tumor-initiating cells, in the most metastatic 4T1 and 66cl4 carcinoma
cell lines. This effect was attainable in carcinoma cell co-culture with the RAW
264.7s, where the metastatic 4T1 and 66cl4 cell lines also formed spheroid
structures amid direct cell contact from the macrophages. A subsequent gene
expression analysis performed on 4T1/RAW 264.7 co-cultures suggested that
the RAW 264.7s induced Sca-1 expression in the metastatic cell lines through
anti-tumoral actions. Finally, a functional study of Sca-1(+) 4T1 cells indicated
that they proliferated faster but tended to be less motile than Sca-1(-) cells in
response to RAW 264.7-conditioned media, further supporting their tumorinitiating
capability. By integrating these findings into a metastatic narrative, this
thesis proposes that macrophages enhance metastasis through the expansion of
a tumor-initiating subpopulation in metastatic mammary carcinoma cell lines.
University of Minnesota M.S. thesis. July 2012. Major: Integrated Bioscience. Advisor:Teresa A. Rose-Hellekant, D.V.M., Ph.D., 1 computer file (PDF); vii, 99 pages.
Berens, Eric Bruce.
RAW 264.7 macrophages induce tumor-initiating behavior in metastatic but not nonmetastatic mammary carcinoma clones..
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