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Secretomes from metastatic breast cancer cells, enriched for a prognostically unfavorable LCN2 axis, induce anti-inflammatory MSC actions and a tumor-supportive premetastatic lung


The cover for issue 32 of Oncotarget features Figure 5, "Model of potential mechanisms by which soluble factors from the primary breast tumors may induce an anti-inflammatory state within premetastatic tissues," by Meade, et al.

Mining transcriptome data from Py8119 and Py230 cells revealed a lipocalin 2 axis that is selectively expressed in the metastatic Py230 cells, predicts poor breast cancer patient survival and is elevated in circulating serum of mice chronically treated with conditioned media from Py230 cells.

Taken together, these results establish the utility of an immune-competent tumor cell-free model for characterizing the mechanisms of breast cancer cell priming of the premetastatic niche, demonstrate that MSCs can mediate the anti-inflammatory effects of metastatic breast cancer cells and substantiate LCN2 as a promising therapeutic target for blocking breast cancer progression.

Dr. Kelber from the Department of Biology, at the California State University Northridge in Northridge CA 91330, USA said "Metastasis is the major cause of most cancer-related deaths."

Metastasis is the major cause of most cancer-related deaths.

Prior to tumor cell arrival, these potential sites of metastasis are termed the premetastatic niche and include a diverse profile of cells and molecules susceptible to pro-tumorigenic reprogramming.

The concept of the premetastatic niche comes from the idea of the seed and soil hypothesis that defines the seed as cells from the primary tumor that colonize the soil, or specific organs, that have been prepared to support their growth.

Also, MSCs are shown to recruit macrophages to the tumor site and stimulate macrophage polarization further driving tumor progression.

Figure 5: Model of potential mechanisms by which soluble factors from the primary breast tumors may induce an anti-inflammatory state within premetastatic tissues. Data presented herein suggest a potential role for primary tumor released soluble factors (e.g., LCN2) that can act via circulation and communicate with bone marrow derived cells (BMDCs) to prime the premetastatic niche toward a tumor-supportive state. Of interest for future work will be the analysis of whether such secreted factors act to remodel the premetastatic niche directly to recruit BMDCs (e.g., liberating mesenchymal stem cells from the perivascular niche) or whether they directly influence the recruitment and/or expansion of BMDCs from circulation.

Although some of the processes by which the primary tumor primes the premetastatic niche have been described, work to date has been predominantly limited to immune-deficient mouse models and the mechanisms by which various resident or newly recruited cell populations may interact during the premetastatic niche reprogramming phase of tumor progression remain poorly understood.

Here, the authors sought to establish a tumor cell-free, immune-competent mouse model for evaluating how secretomes from metastatic versus non-metastatic breast cancer cells differentially remodel the premetastatic niche toward a tumor-supportive state.

The Kelber Research Team concluded, "Finally, it is interesting to note that while previous studies have identified LCN2 as a promising therapeutic target to abrogate progression and metastasis in breast cancer, other work has suggested that LCN2 is not necessary for metastasis.

In this regard, it will be important for future studies to evaluate whether LCN2 is necessary and/or sufficient for promoting a tumor-supportive state within the premetastatic niche."

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DOI - https://doi.org/10.18632/oncotarget.26903

Full text - https://www.oncotarget.com/article/26903/text/

Correspondence to - Jonathan A. Kelber - jonathan.kelber@csun.edu

Keywords - premetastatic niche, tumor microenvironment, metastasis, breast cancer secretomes, LCN2

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