Thread by @sflomos

1/🧵We developed new in vivo #ILC models injecting intraductally ER+ #ILC lines and freshly dissected ER+ ILC tumors @EmboMolMed embopress.org/doi/full/10.15…

2/🧵#ILC cells establish themselves at the ductal tips #microenvironment and form grape-like structures reminiscent of #TDLUs of the human breast.

3/🧵We show that in these models, the tumor cells grow slowly, invade forming hILC histologies, and metastasize in a similar way as they do in patients in clinical relevant organs including ovaries, brain-meninges, adrenal gland, GI tract, liver, and lung.

4/🧵Importantly, stimulation with #E2 by means of a subcutaneous increased #PR indicating that the #ER/PR axis is well preserved.

5/🧵ILC cells spread intraepithelially mirroring the #pagetoid growth characteristic of #lobular carcinomas.

6/🧵Pure PDX derived #ILC cells were sampled and compared with pure #NST-IDC cells and RNAseq. revealed genes involved in #ECM production and organization were highly enriched in RNA from #ILC.

7/🧵ECM remodeling signature identified in the PDXs is also found in TCGA ILC datasets. Remarkably, #LOXL1, responsible for cross-linking of collagens and elastin #ELN, is strongly expressed in #CDH1 neg. #ILC cells.

8/🧵Inhibition/silencing of #LOXL1 results in disrupted collagen fibers, decreased #ER signaling activity, decreased tumor cell proliferation, progression, and metastasis in the intraductal ILC models, and opens up new avenues for #ILC therapy.

9/🧵I express my gratitude and appreciation to mentors @CBrisken and collaborators @PatrikAouad @FabioDeMartin12 @athinastravodi1 @ScabiaValentina @GioAmbrosini314 #BriskenLab and those not (yet) in #Twitter

10/🧵I thank the reviewers for their constructive comments and the stellar editorial process on @EmboMolMed. Many thanks to @FondationIsrec #biltemafoundation # MatsPaulssonstiftelserna @snsf_ch #liguecancer for funding this #ILC project.

11/🧵Special thanks to all patients and their families in #Lausanne for donating #ILC samples, bringing greater benefits to patients. This work is dedicated to Emanuela (Nela) Busz. Her advocacy voice in Europe helped other patients with lobular breast cancer. Rest in strength.