Background: Synapse-associated protein (SAP) 90/Postsynaptic density (PSD)-95-associated protein (SAPAP) (also called Guanylate kinase-associated protein/hDLG-associated protein) interacts with the guanylate kinase domains of PSD-95 and synaptic scaffolding molecule (S-SCAM) via the middle region containing 5 repeats of 14 amino acids. SAPAP also binds the recently identi®ed proteins, nArgBP2 and synamon (also called Shank 1a), via the proline-rich region and the C-terminus, respectively. SAPAP is highly enriched in the Triton X-100-insoluble PSD fraction, and recruits PSD-95 into the Triton X-100-insoluble fraction in transfected cells. We have further characterized here the Triton X-100-insolubility of SAPAP and tried to identify the Triton X-100-insoluble structures which SAPAP interacts with.
Basement membrane matrix proteins, such as matrigel, are able to improve the efficiency of tumour transplantation. This assay represents the gold standard to measure tumour initiation potential in vivo of a limited number of cancer cells. However, in culture conditions, matrigel directly signals to cancer cells altering their phenotype. We here investigate how matrigel influences the tumour reconstitution dynamics of breast cancer cells in vivo. This is particularly relevant in the setting of limiting dilution assay where cells are transplanted in a relatively high amount of Matrigel. We show that matrigel initially induces a normalized growth of transplanted MMTV-PyMT breast tumours cells. This occurs in the context of a matrigel-segregation effect where cancer cells are transiently isolated from host tissue. We identify macrophages as gatekeepers of the cancer-host cell interaction: depriving transplants from macrophages locked cancer cells in this isolated environment where they fail to form tumours despite retaining their intrinsic tumorigenic potential. This is a decisive proof of concept that cancer cells’ malignant behaviour can be dominated by their microenvironment. Moreover, considering that diverse breast cancer cells are differently subjected to a segregation effect, this needs to be considered when comparing tumour initiation potential of different cancer cells.
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