Breast Cancer Case Study

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2.extravasation
For metastatic outgrowth extravasation of tumor cells and secondary seeding are important. In secondary organs fibronectin expression is upregulated by primary tumors via resident fibroblasts, which serves as a docking site for VEGFR1+ hematopoietic progenitor cell (HPC) clusters and secondary seeding. During metastasis of breast cancer to lung, interaction of VCAM-1+ cancer cells with VLA-4-expressing macrophages, activates PI3K/Akt signaling in tumor cells, protecting them from caspase-induced apoptosis. Bone metastasis is also facilitated by interaction of VCAM1 with different integrin partner, α4β1, in osteoclasts. Thus, we can conclude that disruption of adhesion signaling between stromal cells and tumor cells can
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Additional studies mention about how primary tumor hypoxia influences the premetastatic niche. Major BMDC contributors to hypoxia-induced pseudo-premetastatic niche are MDSCs and NK cells with impaired cytotoxicity.(Sceneay, 2012) (Sceneay J, et al. Primary tumor hypoxia recruits CD11b+/Ly6Cmed/Ly6G+ immune suppressor cells and compromises NK cell cytotoxicity in the premetastatic niche. Cancer research. 2012; 72:3906–3911. [PubMed: 22751463])

Organ tropism
The circulating cancer cells that are released from primary tumors leave a micro- environment created by the supportive stroma of such tumors. Creating supportive stroma is a multi – step process, thus in some cases cancer cells seeded in new metastatic niches do not begin by inducing a supportive stroma because it already preexists. Such permissivity may be intrinsic to the tissue site (Talmadge and Fidler, 2010) or pre-induced by circulating factors released by the primary tumor (Peinado et al., 2011).

Metastatic seeding of circulating tumour cells has been shown in some cases to be enhanced by the primary tumour, whose secreted products create an environment that favours establishment of metastases at unique distant sites, termed pre-metastatic niches. The most well-documented components of induced premetastatic niches are tumor-promoting inflammatory

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