Details

Autor(en) / Beteiligte

• Ying Xiong Lindsay T McDonald Dayvia L Russell Ryan R Kelly Katie R Wilson Meenal Mehrotra Adam C Soloff Amanda C LaRue

Titel

Hematopoietic stem cell-derived adipocytes and fibroblastsin the tumor microenvironment

Ist Teil von

• 世界干细胞杂志：英文版（电子版）, 2015 (2), p.253-265

Erscheinungsjahr

2015

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• The tumor microenvironment （TME） is complex andconstantly evolving. This is due, in part, to the crosstalkbetween tumor cells and the multiple cell types thatcomprise the TME, which results in a heterogeneouspopulation of tumor cells and TME cells. This reviewwill focus on two stromal cell types, the cancerassociatedadipocyte （CAA） and the cancer-associatedfibroblast （CAF）. In the clinic, the presence of CAAsand CAFs in the TME translates to poor prognosis inmultiple tumor types. CAAs and CAFs have an activatedphenotype and produce growth factors, inflammatoryfactors, cytokines, chemokines, extracellular matrixcomponents, and proteases in an accelerated andaberrant fashion. Through this activated state, CAAs andCAFs remodel the TME, thereby driving all aspects oftumor progression, including tumor growth and survival,chemoresistance, tumor vascularization, tumor invasion,and tumor cell metastasis. Similarities in the tumorpromotingfunctions of CAAs and CAFs suggest that amultipronged therapeutic approach may be necessaryto achieve maximal impact on disease. While CAAsand CAFs are thought to arise from tissues adjacentto the tumor, multiple alternative origins for CAAs andCAFs have recently been identified. Recent studiesfrom our lab and others suggest that the hematopoieticstem cell, through the myeloid lineage, may serve asa progenitor for CAAs and CAFs. We hypothesize thatthe multiple origins of CAAs and CAFs may contributeto the heterogeneity seen in the TME. Thus, a betterunderstanding of the origin of CAAs and CAFs, howthis origin impacts their functions in the TME, and the temporal participation of uniquely originating TME cells may lead to novel or improved anti-tumor therapeutics.