Effect of Host-Organ Environment on the in vivo and in vitro Behavior of a Murine Mammary Adenocarcinoma

Puricelli, Lydia; Gómez, Daniel E.; Vidal, M; Eiján, Ana María; Spinelli, Olga; Alonso, Daniel F.; Lustig, Eugenia Sacerdote de; Joffé, Elisa Bal de Kier

doi:10.1159/000217903

Cited by 7 publications

(5 citation statements)

References 8 publications

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“…These results confirm previous data showing that lung-derived factors enhance the prolifer ation and migration in vitro, the local and metastatic growth in vivo [24] as well as the uPA activity [25] of M3 cells.…”

Section: Discussionsupporting

confidence: 92%

Effects of in vivo Culture of Murine Mammary Adenocarcinoma Cells on Tumor and Metastatic Growth

Ghiso

Diament

D'Elia³

et al. 1997

Tumor Biol

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We studied the effect of tumoral microenvironments on metastatic phenotypes. Therefore, murine mammary adenocarcinoma cells cultured in vivo in diffusion chambers (DC) were implanted intraperitoneally in BALB/c mice. The behavior of DC-cultured cells was compared with that of cells obtained from tumors growing subcutaneously or intraperitoneally and from primary cultures in vitro of the former. DC-cultured and control cells were inoculated into normal mice to evaluate their tumorigenicity and metastasizing ability. We found that DC-cultured cells were less tumorigenic and metastatic both in spontaneous and in experimental metastasis assays. The host reponse to tumor progression resulted in an early leukocytosis, probably due to the overproduction of a hematopoietic factor by the tumor cells. Finally, it was found that DC-cultured cells produced lower levels of urokinase-type plasmino-gen activator activity, while no differences were found in the metalloproteinase production compared to cells obtained from a tumor growing subcutaneously.

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Section: Discussionsupporting

confidence: 92%

Effects of in vivo Culture of Murine Mammary Adenocarcinoma Cells on Tumor and Metastatic Growth

Ghiso

Diament

D'Elia³

et al. 1997

Tumor Biol

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“…To assay their spontaneous metastatic ability, M3 and MM3 cells, harvested from subconfluent primary cultures during the exponential growth phase by treatment with Trypsin-EDTA, were washed thoroughly with MEM and resuspended in the same medium. Non-anesthetized BALB/c female mice were inoculated s.c. into the left flank with 2x10 5 viable cells of each tumor type, in a volume of 200 μl of serum-free MEM. Six weeks after inoculation animals were sacrificed and lungs were fixed in Bouin's solution.…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, the molecular requirements for some of these steps may be tissue specific. In fact, the proclivity that some tumors have for specific organs, such as breast carcinomas for bone and lung, was described more than a century ago and is still a matter of analysis (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Fibronectin is distinctly downregulated in murine mammary adenocarcinoma cells with high metastatic potential

Urtreger

Werbajh²,

Verrecchia³

et al. 2006

Oncol Rep

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Abstract. In the present work we used a murine mammary cancer model of two related adenocarcinomas with different lung metastasizing abilities, to compare their global gene expression profiles. Clontech Atlas mouse cDNA microarrays of primary cultured tumor cells were employed to identify genes that are modulated in the more metastatic variant MM3 relative to its parental tumor M3. A total of 88 from 1,176 genes were differentially expressed in MM3 primary cultures, most of them (n=86) were upregulated. Genes were grouped according to their functions as associated with signal transduction and transcription regulation (e.g. Stat1 and Zfp 92), with cell adhesion and motility (cadherin 1, fibronectin), with invasion and angiogenesis (uPA, 72 kDa MMP2), with the regulation of cell proliferation and cell death (cyclins G and A2, TNF), and also included growth factors and receptors, oncogenes and tumor suppressors genes (p107, TGFß2, TBR-I, PDGFR). Only 2 genes, TTF1 and fibronectin (FN), showed a significant downregulation. Notably FN expression, loss of which has been associated with a malignant phenotype, was reduced about 19-fold in the more metastatic MM3 cells. Previously known differences in expression patterns associated with the metastatic capacity of MM3 and M3 adenocarcinomas, including downregulation of FN or upregulated expression of TGFß and proteases, were confirmed by the array data. The fact that FN was one of the only two genes significantly down-regulated out of the 1,176 genes analyzed stresses the hypothesis that FN may behave as an important metastasis suppressor gene in mammary cancer. IntroductionThe major pathological effect of cancer is caused by the invasion of malignant cells to surrounding tissues and the subsequent metastasis to vital organs. The metastatic process involves the detachment and infiltration of the cells from the original primary tumor, intravascular invasion, transportation in the blood, arrest in the microvasculature, extravasation, and finally, proliferation at the target organ (1,2). This process involves the participation of numerous molecules with specific activities, such as growth factors and their specific receptors, cell adhesion molecules, cytoskeleton proteins, extracellular matrix components (ECM) as fibronectin (FN), and proteolytic enzymes such as plasminogen activators (uPA) and metalloproteinases (MMP) (3). Moreover, the molecular requirements for some of these steps may be tissue specific. In fact, the proclivity that some tumors have for specific organs, such as breast carcinomas for bone and lung, was described more than a century ago and is still a matter of analysis (4-6).It is accepted that tumors are heterogeneous for many properties and contain subpopulations of more or less aggressive cells that differ in many of their biochemical and biological characteristics, such as growth rate, karyotype, expression of hormone receptors, and their invasive and metastatic capability (7). Taking advantage of this characteristic, many experimental models, useful t...

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“…We have shown that soluble factors from the lung, the target organ for the dissemination of the murine mammary adenocarcinoma cell line LM3, could enhance local and metastatic growth when inoculated together with the tumor cells intravenously or separately via intra peritoneal [59]. We also showed that the lung conditioned media stimulated in vitro growth and migration of tumor cells and secreted uPA activity in addition to enhancing angiogenesis in vivo [59][60][61]. Moreover, the microenvironment can exert a reprogramming effect.…”

Section: Growing In the Secondary Organmentioning

confidence: 91%

Cross-Talk between Tumor Cells and the Microenvironment at the Metastatic Niche

Carlini

Lorenzo²,

Puricelli³

2011

CPB

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This review presents recent information about the cross-talk between the tumor cells and the microenvironment in the target organ of metastasis at the premetastatic and metastatic stage. The development of metastatic foci is driven not only by the tumor cells intrinsic properties, but also by the interplay with resident and foreign cells located at particular niches in the target organ. The primary tumor modulates the metastatic target through the production of soluble factors that mobilize cells from distant organs like the bone marrow, which in turn localize in the metastatic niche. There is also strong evidence indicating that some primary tumors induce a fertile ground for the tumor cell at the target organ even before the arrival of the disseminated tumor cell (premetastatic niche). The relationship between the players of the metastatic setting is dynamic and shows a high degree of plasticity. Tumor cells change through the acquisition of genetic and/or epigenetic alterations that provide adaptive advantages and the metastatic niche is remodeled by incoming cell types or newly secreted soluble mediators, as a result a reciprocal dialogue is established that invokes new levels of molecular and cellular complexity. Unraveling the mechanisms that sustain the metastatic niche will allow a better understanding of the biology of the disseminated tumor cell, the design of new therapeutic approaches and, hopefully, the improvement of cancer patients' survival.

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Effect of Host-Organ Environment on the in vivo and in vitro Behavior of a Murine Mammary Adenocarcinoma

Cited by 7 publications

References 8 publications

Effects of in vivo Culture of Murine Mammary Adenocarcinoma Cells on Tumor and Metastatic Growth

Effects of in vivo Culture of Murine Mammary Adenocarcinoma Cells on Tumor and Metastatic Growth

Fibronectin is distinctly downregulated in murine mammary adenocarcinoma cells with high metastatic potential

Cross-Talk between Tumor Cells and the Microenvironment at the Metastatic Niche

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